AU2001253363A1

AU2001253363A1 - Polycyclic aryl and heteroaryl substituted 1,4-quinones useful for selective inhibition of the coagulation cascade

Info

Publication number: AU2001253363A1
Application number: AU2001253363A
Authority: AU
Inventors: John J. Parlow; Michael S. South
Original assignee: Pharmacia LLC
Current assignee: Pharmacia LLC
Priority date: 2000-04-17
Filing date: 2001-04-10
Publication date: 2001-10-30
Also published as: US20030225086A1; CA2405684A1; WO2001079155A3; US20020010344A1; JP2004501077A; US20040171839A1; WO2001079155A2; US6686484B2; EP1274676A2; US20040171616A9

Description

Polycyclic Aryl and Heteroaryl Substituted 1,4-Quinones Useful for Selective Inhibition of the Coagulation Cascade

Field of the Invention

This invention is in the field of anticoagulant therapy, and specifically relates to compounds, compositions and methods for preventing and treating thrombotic conditions such as coronary artery and cerebrovascular disease. More particularly, the invention relates to polycyclic aryl and heteroaryl substituted 1,4-quinone compounds that inhibit serine proteases of the coagulation cascade.

Background of the Invention

Physiological systems control the fluidity of blood in mammals

[Majerus, P. W. et al: Anticoagulant, Thrombolytic, and Antiplatelet Drugs. In Hardman, J. G. and Limbird, L. E., editors: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th edition. New York, McGraw-Hill Book Co., 1996, pp. 1341-1343]. Blood must remain fluid within the vascular systems and yet be able to undergo hemostasis, cessation of blood loss from a damaged vessel, quickly. Hemostasis or clotting begins when platelets first adhere to macromolecules in subendothelian regions of an injured and/or damaged vessels. These platelets aggregate to form the primary hemostatic plug and stimulate local activation of plasma coagulation factors leading to generation of a fibrin clot that reinforces the aggregated platelets.

Plasma coagulation factors include factors II, V, VII, VIII, IX, X, XI, and XII; these are also called protease zymogens. These coagulation factors or protease zymogens are activated by serine proteases leading to coagulation in a so called "coagulation cascade" or chain reaction [Handin, R. I.: Bleeding and Thrombosis. In Wilson, J., et al. editors: Harrison's Principles of Internal

Medicine. 12th Edition, New York, McGraw-Hill Book Co., 1991,p.350]. Coagulation or clotting occurs in two ways through different pathways. An intrinsic or contact pathway leads from XII to Xlla to XIa to IXa and to the conversion of X to Xa. Xa with factor Va converts prothrombin (II) to thrombin (Ila) leading to conversion of fibrinogen to fibrin. Polymerization of fibrin leads to a fibrin clot. An extrinsic pathway is initiated by the conversion of coagulation factor VII to Vila by Xa. The presence of Tissue Factor and Vila accelerates formation of Xa in the presence of calcium ion and phospholipids. Formation of Xa leads to thrombin, fibrin, and a fibrin clot as described above. The presence of one or more of these many different coagulation factors and two distinct pathways of clotting could enable the efficacious, selective control and better understanding of parts of the coagulation or clotting process.

While clotting as a result of an injury to a blood vessel is a critical physiological process for mammals such as man, clotting can also lead to disease states. A pathological process called thrombosis results when platelet aggregation and/or a fibrin clot blocks (i.e., occludes) a blood vessel. Arterial thrombosis may result in ischemic necrosis of the tissue supplied by the artery. When the thrombosis occurs in a coronary artery, a myocardial infarction or heart attack can result. A thrombosis occurring in a vein may cause tissues drained by the vein to become edematous and inflamed. Thrombosis of a deep vein may be complicated by a pulmonary embolism. Preventing or treating clots in a blood vessel may be therapeutically useful by inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, inhibiting embolus formation, and for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels.

There have been several reports of non-peptidic and peptidic 2-pyridone compounds that act as an inhibitor of a coagulation factor present in the coagulation cascade or clotting process. In US Patent 5,668,289, Sanderson et al. describe 6-alkyl, 6-cycloalkyl, and 6-trifluoromethyl 2-ρyridones unsubstituted at the 4 and 5 positions and reported to inhibit thrombin. In PCT Patent Application WO 97/01338, Sanderson et al. describe 6-alkyl, 6- cycloalkyl, and 6-trifluoromethyl 2-pyridones unsubstituted at the 4 and 5 positions and reported to inhibit thrombin. In US Patent 5,792,779, Sanderson etal. describe substituted 4,6-alkyl, 4,6-cycloalkyl, and 4,6-trifluoromethyl 2- pyridones having utility as thrombin inhibitors. In PCT Patent Application WO 97/30708, Sanderson et al. describe additional substituted 4,6-alkyl, 4,6- cycloalkyl, and 4,6-trifluoromethyl 2-pyridones having utility as thrombin inhibitors. In US Patent 5,869,487, Coburn et al. describe pyrido[3,4- B]pyrazines containing a fused 6-methyl-2-pyridone functionality and having utility as thrombin inhibitors. In PCT Patent Application WO 98/47876, Van Boeckel et al. describe 6-alkyl-2-pyridones as anti-thrombotic compounds. In PCT Patent Application WO 98/16547, Zhu and Scarborough describe 4,5,6- substimted-3-amino-2-pyridonylacetarnides containing amide substituents having a heteroaroyl functions and having activity against mammalian factor Xa. In US Patent 5,656,645, Tamura et al. describe 4,5,6-substituted-3-amino-2- pyridonyl-acetamides containing amide substituents having a formyl function and having activity against thrombin. In US Patent 5,658,930, Tamura et al. again describe 4,5,6-substituted-3-amino-2-pyridonyl-acetamides containing amide substituents having a formyl function and having activity against thrombin. In PCT Patent Applications 96/18644, Tamura et al. further describe 4,5,6-substituted-3-amino-2-pyridonylacetamides containing amide substituents having a formyl function and having activity against thrombin. In PCT Patent Application WO 98/31670, Sanderson et al. describe additional 4-substituted 6-alkyl, 6-cycloalkyl, and 6-trifluoromethyl pyridones having utility as thrombin inhibitors. In PCT Patent Application WO 98/17274, Coburn et al. disclose substituted 3,4-diamino-6-methyl-2-pyridones having utility as human thrombin inhibitors. In PCT Patent Application WO 98/42342, Isaacs et al. describe additional 6-alkyl, cycloalkyl, and trifluoromethyl substituted 2- pyridones reported to inhibit human thrombin.

In contrast to the disclosures that some 2-pyridone derivatives may function as thrombin inhibitors, 4-pyronyl compounds, compositions thereof, their use for preventing and treating thrombotic conditions such as coronary artery and cerebrovascular disease, and their ability to inhibit serine proteases of the coagulation cascade have not been previously disclosed.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel compounds that are beneficial in anticoagulant therapy and that have a general structure: Formula (I).

It is another object of the present invention to provide methods for preventing and treating thrombotic conditions, such as coronary artery disease, cerebrovascular disease, and other coagulation related disorders. Such thrombotic conditions are prevented and treated by administering to a patient in need thereof an effective amount of compounds of Formula (I).

Various other objects and advantages of the present invention will become apparent from the following description of the invention.

DESCRIPTION OF THE INVENTION

The present invention relates to a class of compounds comprising Polycyclic Aryl and Heteroaryl Substituted 1,4-quinones, which are beneficial in anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular disease, as given in Formula (I):

or a pharmaceutically acceptable salt thereof, wherein; B is formula (V):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one can be a covalent bond, no more than one of D , D , J , J and K

1 2 1 2 1 1 2 can be O, no more than one of D , D ,J , J andK can be S, one of D ,D ,

1 2 1 1 2 1 ,2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 2 1

O and S, and no more than four of D ,,DD ,,JJ ,,r J , and ^' K^" can be N with the

32 33 34 35 36 proviso that R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

32 33 34 35 36 b

R ,R ,R ,R ,andR can independently be Q ; n9 10 11 12 13 16 17 18 19.32 33 34 35 _J R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,and

36 R are independently selected from the group consisting of hydπdo, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylarnino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, a ino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxy alkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfmylalkyl, arylsulfonylalkyl, heteroarylsulfmylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsuliϊnylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl ;

_^32 , 33 „33 , „34 34 , 35 , 35 _Λ 36

R an R , R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group 32 33 33 34 34 35 35 consisting of spacer pairs R andR ,R andR ,R andR ,andR

and R can be used at the same time; τ,9 _^10 _^10 _Jnll 11 12 12 _JT,13

R andR ,R andR ,R andR ,andR andR can be independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group

9 10 10 11 11 12 12 consisting of spacer pairs R andR ,R andR ,R andR ,andR

13 and R can be used at the same time;

B can be formula (VI):

3 4 4 wherein D ,D , J ,andj are independently selected from the group consisting of

3 4 3 4

C, N, O, and S, no more than one of D , D , J , and J can be O, no more than one

^ 4 4 1 9 1 9 of D , D , J , and J can be S, and no more than three of D , D , J , and J can

32 33 34 35 be N with the proviso that R ,R ,R ,andR are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R32, R33, R34, R35, and R^Q;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5- C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R23, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

R JQ, a ring carbon or nitrogen atom adjacent to the R ^3 position and two atoms

from the point of attachment may be substituted with R _j2, ^a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_{j j} , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R^ position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34;

7 A is selected from the group consisting of single covalent bond, (W )_rr-

15 15 7

(CH(R ))_pa and (CH(R )) _a-(W )_n wherein π is an integer selected from

7 0 through 1, pa is an integer selected from 0 through 6, and W is selected

from the group consisting of O, S, C(O), C{S), C(O)S, C(S)O, C(O)N(R^?),

C(S)N(R⁷), (R^?)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R^?)NS(O)₂, Se(O), Se(O)₂, Se(O)₂N(R^?), (R⁷)NSe(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸), P(O)(R⁸)N(R^?), C(NR^?)N(R⁷), (R⁷)NC(NR^?), and N(R^?);

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, alkylamino, arylthio, arylamino, acyl, aroyl, heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl, , aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkyloxy, heteroaralkylamino, and heteroaryloxyalkyl;

„ 14 15 37 38 39 40 41 , . 42 . _J

R , R , R , R , R ,R , R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxy thioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfmylalkyl, aralkylsulfmylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, trialkylsilyl, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and di aralkoxyphosphonoalkyl ;

14 14

R and R , when bonded to different carbons, can be taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

14 15 R and R , when bonded to different carbons, can be taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of a cycloalkyl ring having from 5 through 8 contiguous members, a cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

15 15

Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

5 8 39 40

S(O), S(O)₂, ON(R ), P(O)(R ), and CR R ;

5 R is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, arylthio, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, and dialkoxyphosphonoalkyl;

39 40 R and R , when bonded to the same carbon, can be taken together to

form a group selected from a group consisting of oxo, thiono, R -N, alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

Λ and R are independently selected from the group consisting of Z -

Q, hydrido, alkyl, alkenyl, and halo; o

X and R can be independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono;

Λ and R can be taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members; o 39

X and R can be taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members;

JO 40

Λ and R can be taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members; X can be independently selected to form a linear moiety having from 2

39 through 5 contiguous atoms linked to the points of bonding of both R and

40 R to form a heterocyclyl ring having from 5 through 8 contiguous members;

R² and R⁴ , R² and R^4b, R² and R¹⁴, and R² and R¹⁵ can be independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members with the

2 proviso that no more than one of the group of spacer pairs consisting of R and

4a ? 4b 14 9 15

R , R and R , R and R , and R and R can be used at the same time;

R can be independently selected to form a linear moiety having from 2

4a through 5 contiguous atoms linked to the points of bonding of both R and

4b R to form a heterocyclyl ring having from 5 through 8 contiguous members;

Z is selected from the group consisting of covalent single bond,

41 42 41 (CR R )_q wherein q is an integer selected from 1 through 6, (CH(R ))„- o 42

W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O, S, C{0), C(S),

41 41 41

C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ), (R )NC(O), C(S)N(R ),

41 41 41 41 41

(R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ), (R )NC(S)S,

41 41 41 41

SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

42 41 41 42 42 41 N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ),

(R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹), N(R⁴¹)S(O)₂, Se, Se(O),

Se(O)₂, Se(O)₂N(R⁴¹), N(R⁴¹)Se(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸),

8 7 41 41 28 29 41 2

P(O)(R )N(R ), N(R ), ON(R ), and SiR R , and (CH(R ))_e-W -

42 (CH(R )) _j wherein e and h are integers independently selected from 0

2 41 42 through 2 and W^{^} is selected from the group consisting of CR =CR ,

41 42 CR R =C; vinylidene), and ethynylidene (C≡C; 1,2-ethynyl), with the

41 42 proviso that R and R are selected from other than halo and cyano when directly bonded to N and Z is directly bonded to the quinone ring; Q is formula (II):

consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 1 2 can be O, no more than one of D , D ,J ,J andK can be S, one of D ,D ,

1 2 1 1 2 1 2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 2 1

O and S, and no more than four of D ,D ,J ,J andK can be N, with the

9 10 11 12 13 proviso that R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; Q can be formula (III):

3 4 /5 4 wherein D , D , J , and J are independently selected from the group

3 4 3 4 consisting of C, N, O, and S , no more than one of D , D , J , and J can be O,

3 4 4 i no more than one of D , D , J , and J can be S, and no more than three of D , 2 1 J2 9 10 11 12

D , J , and J can be N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; Q can be selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxy alkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl;

4a 4b K is (CR R )_n wherein n is an integer selected from 1 through 4;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfinyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, and aralkylsulfonylalkyl;

4a 4b R and R , when bonded to the same carbon, can be taken together to form a group selected from the group consisting of oxo, thiono, and a linear spacer moiety having from 2 through 7 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkyl ring having 3 through 8 contiguous members, a cycloalkenyl ring having 5 through 8 contiguous members, and a heterocyclyl ring having 5 through 8 contiguous members; o 1 4a 4b 1

E is E , when K is (CR R )_n, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), OC(O)N(R^?),

(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R^?), (R⁷)NC(O)S,

OC(S)N(R⁷), (R^?)NC(S)O, N(R⁸)C(O)N(R⁷), (R^?)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R^?), N(R^?)S(O)₂,

S(O)₂N(R⁷)C(O), C(O)N(R^?)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R^?),

N(R⁷)Se(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸), P(O)(R⁸)N(R^?), N(R⁷), ON(R^?),

28 29 4a 4b 4a 4b

SiR R , CR =CR , ethynylidene (CsC; l,2-ethynyl), and C=CR R ;

28 29 R and R are independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyi, carboalkoxyaikyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfmylalkyl, arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl and diaralkoxyphosphonoalkyl;

28 29

R and R can be taken together to form a linear moiety spacer having from 2 through 7 contiguous atoms and forming a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

14 K can be (CH(R ));-T wherein j is selected from a integer from 0 through 3 and T is selected from the group consisting of single covalent bond,

7 14 O, S, and N(R ) with the proviso that (CH(R )) is bonded to the quinone ring; E IS E , when K is (CH(R ));-T, where E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R⁷), (R^?)NC(S), (R⁷)NC(O)O,

(R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R^?)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R^?), N(R^?)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, Se(O),

Se(O)₂, Se(O)₂N(R⁷), N(R^?)Se(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸),

P(O)(R⁸)N(R^?), and N(R^?);

15 K can be G-(CH(R ))_jc wherein k is selected from an integer from 1

7 through 3 and G is selected from the group consisting of O, S, and N(R ) with

15 the proviso that R is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1;

E is E when K is G-(CH(R ))_j, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R⁷)NC(O), C(S)N(R^?), (R⁷)NC(S),

OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R^?), (R⁷)NC(S)S, SC(O)N(R⁷),

(R⁷)NC(O)S, OC(S)N(R^?), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R^?)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R⁷), N(R⁷)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R^?), N(R^?)Se(O)₂,

8 7 8 8 7 7 7 28 29 P(O)(R ), N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), SiR R ,

CR^4a=CR^4b, ethynylidene (C=C; 1,2-ethynyl), and C=CR^4&R^4b; Y° is formula (IV):

5 6 5 6 wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one can be a covalent bond, K is independently selected from the group

consisting of C, and N , no more than one of D , D , J , and J can be O, no ι _ ,_ 5 6 5 6 ,-_^5 _^6 5 _τ6 more than one of D , D , J , an J can be S, one of D , D , J , and J must

5 6 i 6 be a covalent bond when two of D , D , J , and J are O and S, no more than

5 6 5 6 2 + three of D , D , J , and J can be N when K is N , and no more than four of J J , _xτ , _T 2 . , . , , . , 16 D , D , J , and J can be N when K is carbon with the provisos that R ,

17 18 19

R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

R and R can be independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl;

18 19 R and R can be independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl; b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,

20 ammoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino

20 21 22 and that R , R , and R must be other than be hydroxy, alkoxy,

2 + alkylamino, ammo, and dialkylamino when K is N ;

20 21 20 22 21 22

R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 4 through 7 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having 5 through 8 contiguous members with the proviso that no more than one of the

20 21 20 22 21 22 group consisting of spacer pairs R and R , R and R , and R and R can be used at the same time;

Q can be selected from the group consisting of

N(R²⁶)SO₂N(R²³)(R²⁴), N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, 6 5 96 5

N(R )C(S)OR and N(R )C(S)SR with the proviso that no more than one

23 24 26 of R , R , and R can be hydroxy, alkoxy, alkylamino, amino, or

23 24 26 dialkylamino when two of the group consisting of R , R , and R are bonded to the same atom; Q can be selected from the group consisting of dialkylsulfonium,

trialkylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,

C(O)N(R )C(NR )N(R )(R ), C(S)N(R )C(NR )N(R )(R ),

26 26 25 23 24 26 26 23 24

N(R )N(R )C(NR )N(R )(R ), N(R )N(R )SO₂N(R )(R ),

25 5 23 24 23 24

C(NR )SR , C(O)NR R , and C(O)NR R with the provisos that no i2 94 more than one of R , R , and R can be hydroxy, alkoxy, alkylamino,

23 24 26 amino, or dialkylamino when two of the group consisting of R , R , and R b are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

23 24 25 26

R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;

23 24

R and R can be taken together to form a linear spacer moiety having from 4 through 7 contiguous atoms connecting the points of bonding to form a heterocyclyl ring having 5 through 8 contiguous members;

23 25 24 25 25 26 24 26 23 26 R and R , R and R , R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group consisting of O, S, C(O), C(S), C(J_H)₂ S(O), SO₂, OP(OR³¹)R³⁰, P(O)R³°, P(S)R³°, C(R³⁰)R³¹ , C=C(R³⁰)R^{3 X} , (O)₂POP(O)₂, R³°(O)POP(O)R³°, Si(R²⁹)R²⁸, Si(R²⁹)R²⁸Si(R²⁹)R²⁸, Si(R²⁹)R²⁸OSi(R²⁹)R²⁸,

(R²⁸)R²⁹COC(R²⁸)R²⁹, (R²⁸)R²⁹CSC(R²⁸)R²⁹, C(O)C(R³⁰)=C(R³¹),

C(S)C(R³°)=C(R³¹), S(O)C(R³⁰)=C(R³¹), SO₂C(R³⁰)=C(R³¹),

30 30 31 30 30 31 30 30 31

PR C(R )=C(R ), P(O)R C(R )=C(R ), P(S)R C(R )=C(R ), DC(R³°)(R³¹)D, OP(OR³¹)R³°, P(O)R³°, P(S)R³⁰, Si(R²⁸)R²⁹ and N(R³⁰), and a covalent bond with the proviso that no more than any two of L, U and V are simultaneously covalent bonds and the heterocyclyl comprised of by L, U, and V has from 5 through 10 contiguous member;

D is selected from the group consisting of oxygen, C=O, C=S, S(O)_m wherein m is an integer selected from 0 through 2;

27 27 J_H is independently selected from the group consisting of OR , SR and

N(R²°)R²¹;

27 R is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsulfonylalkyl ;

30 31

R and R are independently selected from hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, heteroaryloxyalkyl, alkoxy, aikylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloaralkylsulfinylalkyl, aralkylsulfonylalkyl, cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyi, carboalkoxyaikyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, phosphonoalkyl, dialkoxyphosphonoalkoxy, diaralkoxyphosphonoalkoxy, phosphonoalkoxy, dialkoxyphosphonoalkylamino, diaralkoxyphosphonoalkylamino, phosphonoalkylamino, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, sulfonylalkyl, alkoxysulfonylalkyl, aralkoxysulfonylaϊkyl, alkoxysulfonylalkoxy, aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino, aralkoxysulfonylalkylamino, and sulfonylalkylamino;

R and R can be taken to form a linear moiety spacer group having from

2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from

3 through 8 contiguous members;

23 25 24 25 25 26 24 26 23 26

R and R , R and R , R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of 1,2- disubstituted radicals consisting of a cycloalkyl radical, a cycloalkenyl radical wherein cycloalkyl and cycloalkenyl radicals are substituted with one or more

30 31 groups selected from R and R , an aryl radical, an heteroaryl radical, a saturated heterocyclic radical and a partially saturated heterocyclic radical wherein said 1,2- substitutents are independently selected from C=O, C=S, C(R )R , S(O),

S(O)₂, OP(OR³¹)R³°, P(O)R³°, P(S)R³° and Si(R²⁸)R²⁹;

23 25 24 25 25 26 24 26 23 26

R and R , R and R , R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of radicals consisting of 1,2-disubstituted alkylene radicals and 1,2-disubstituted alkenylene radical wherein said 1,2-substitutents are independently selected from

9R 9Q 31 30 30 30

C=O, C=S, C(R )R , S(O), S(O)₂, OP(OR )R , P(O)R , P(S)R , and

28 29 Si(R )R and said alkylene and alkenylene radical are substituted with one or more R or R substituents; c

Q is selected from the group consisting of a single covalent bond,

(CR R )tø-(W )_az wherein az is an integer selected from 0 through 1, b is an integer selected from 1 through 4, and W is selected from the group consisting ofO, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

14 14 14 14 14

(R )NC(O), C(S)N(R ),(R )NC(S), OC(O)N(R ), SC(S)N(R ),

14 14 15 14 14 15 SC(O)N(R ),OC(S)N(R ),N(R )C(O)N(R ),(R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ),(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁷),N(R¹⁴)Se(O)₂,P(O)(R⁸),

7 8 8 7 14 14 2829 N(R )P(O)(R ),P(O)(R)N(R ),N(R ),ON(R ),andSiR R ,

14 1 15

(CH(R ))_C-W -(CH(R ))_j wherein c and d are integers independently

1 selected from 1 through 4, and W is selected from the group consisting of O,

S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O),

14 14 14 14 14 C(S)N(R ), (R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ),

14 14 14 14 14

(R )NC(S)S, SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),

(R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, Se, Se(O),

14 14 8 7 8

Se(O)₂, Se(O)₂N(R ), N(R )Se(O)₂, P(O)(R ), N(R )P(O)(R ),

8 7 14 14 28 29 14 2 P(O)(R )N(R ), N(R ), ON(R ), SiR R , and (CH(R ))_e-W -

15 (CH(R ))_jj wherein e and h are integers independently selected from 0

2 4a 4b through 2 and W^{^} is selected from the group consisting of CR =CR ,

4a 4b 14 ethynylidene (G≡C; 1,2-ethynyl), and C=CR R with the provisos that R

15 and R are selected from other than halo and cyano when directly bonded to

37 38 14 14 a N and that (CR R )_b, (CH(R ))_C, (CH(R ))_e and are bonded to E ;

37 37

R and R , when bonded to different carbons, can be taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

37 38 R and R , when bonded to different carbons, can be taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

38 38

37 38

R and R , when bonded to the same carbon, can be taken together to form a group selected from a group consisting of oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members; 0 b SS ss

Y can be Q -Q wherein Q is selected from the group consisting of

37 38 14 (CR R )f wherein f is an integer selected from 1 through 6, (CH(R ))_c-

1 15

W -(CH(R ))_(j wherein c and d are integers independently selected from 1

through 4, and W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,

C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R^M),

14 14 14 14 14 (R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S, 14 14 15 14 14 15

OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁴), N(R¹⁴)Se(O)₂, P(O)(R⁸),

7 8 8 7 14 14 28 29

N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), SiR R , and

14 2 15 (CH(R ))_e-W^{^}-(CH(R ))_n wherein e and h are integers independently

selected from 0 through 2 and W^ is selected from the group consisting of

4a 4b 4a 4b

CR =CR , ethynylidene (C=C; 1,2-ethynyl), and C=CR R with the

14 15 provisos that R and R are selected from other than halo and cyano when

37 38 1 15 directly bonded to N and that (CR R )_f, (CH(R ))_c, and (CH(R ))_e are bonded to E ; r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1 -cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cycloρentyl, 23- morpholinyl, 2,4-mo holinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4- morpholinyl, 3,5-morρholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 13- pyπolidinyl, 23-pyrrolidinyl, 2,4-pyrrolidinyl, 2,Spyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-ρyranyl, 2H-2,4-ρyranyl, 2H-2,5-pyranyl, 4H-2,3-ρyranyl, 4H-2,4- pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H- pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahydropyranyl, 2,4- tetiahydropyranyl , 2,Stetrahydropyranyl , 2,6-tetrahy dropyranyl , 3 ,4-

38 tetiahydropyranyl, and 3, 5-tetrahy dropyranyl with the proviso that (CH(R ))_r is bonded to E and Q is bonded to lowest numbered substituent position of

each W^*^ ;

Y can be Q -Q wherein Q is (CH(R ))_r- W , r is an integer

4 selected from 1 through 3 , and W is selected from the group consisting of 1 ,2- cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-morρholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6- morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piρerazinyl, 1,3-ρiperazinyl, 1,4-piρerazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4- pyrrolidinyl, 2H-23-ρyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-ρyranyl, 4H-2,5-ρyranyl, 2H-pyran-2-one-3,4-yl, 2H-ρyran-2-one-4,5- yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahy dropyranyl, 2,Stetrahydropyranyl, 2,6-tetrahy dropyranyl, 3,4-

38 tetrahydropyranyl, and 3,5-tetrahydropyranyl with the provisos that (CH(R ))_r

is bonded to E and Q is bonded to highest number substituent position of

4 eachW ;

38 Y can be Q -Q ^s wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzotbiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1 ,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naρhthyl, 1,8- naphthyi, 2,4-naρhthyl, 2,5-naρhthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3 ,5-isoquinolinyl, 3 ,6-isoquinoIinyl, 3 ,7-isoquinolinyl, 3 ,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnoMnyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W and that (CH(R ))_r is bonded to E°;

i can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3 ,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothioρhenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothioρhenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,Sindolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2, isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naρhthyl, 1,7-naρhthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3, quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinoIinyl, 4,8-quinolinyl, 1,4-isoquinolinyI, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinoIinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E .

In an embodiment of compounds of Formula I or a pharmaceutically acceptable salt thereof, B is formula (V):

1 2 1 1 1 2 can be O, no more than one of D , D , J , J and K can be S, one of D , D ,

1 9 1 1 2 1 2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 1

O and S, and no more than four of D , DD ,, JJ ,, r J and K can be N with the

„32 _π33 34 35 _{J n}36 . _{J J} , , R , R , R , R , and R can independently be Q ; 9 10 11 12 13 16 17 „18 „19 _π32 33 34 35 _J R , R , R , R , R , R , R , R , R , R , R , R , R , and

36 R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;

32 33 33 34 34 35 35 36

R and R , R and R , R and R , and R and R can be independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group

32 33 33 34 34 35 35 consisting of spacer pairs R and R , R and R , R and R , and R

and R can be used at the same time;

_«9 , _^ 10 _^10 1 1 11 12 12 13

. . . . „9 _{J T} 0 10 11 1 1 12 12 consisting of spacer pairs R and R , R and R , R and R , and R

13 and R can be used at the same time;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R , R33, R34, R35, and R36;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5- C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R 3, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ, a ring carbon or nitrogen atom adjacent to the R 3 position and two atoms

from the point of attachment may be substituted with R_j2, a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_{j j}, a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j2 position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R and R33 positions may be

substituted with R34;

A is selected from the group consisting of single covalent bond, π 1 ^ 1 ^ϊ 1 ( W )_rr-(CH(R ))_pa and (CH(R ))_pa-(W )„. wherein rr is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O,

C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R^?), C(NR^?)N(R⁷),

(R⁷)NC(NR^?), and N(R^?);

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;

14 15 37 38

R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

5 8 39 40 S(O), S(O)₂, ON(R ), P(O)(R ), and CR R ;

R is selected from the group consisting of hydrido, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, and heteroaroyl;

39 40

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

X and R are independently selected from the group consisting of Z - Q, hydrido, alkyl, alkenyl, and halo;

0 9 X and R can be independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono; Z is selected from the group consisting of covalent single bond,

41 42 41 (CR R )_q wherein q is an integer selected from 1 through 6, (CH(R ))_g- o 42

W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O, S, C(O), C(S),

41 41 41

C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ), (R )NC(O), C(S)N(R ),

41 41 41 41 41 (R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ), (R )NC(S)S,

41 41 41 41

SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

42 41 41 42 42 41 N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ), 41 42 41 41 8

(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ), N(R )S(O)₂, P(O)(R ),

7 8 8 7 41 41 41 2

N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), and (CH(R ))_e-W^-

42 (CH(R ))_b wherein e and h are integers independently selected from 0

2 41 42 through 2 and W^{^} is selected from the group consisting of CR =CR ,

41 42 CR R =C; vinylidene), and ethynylidene (C≡C; 1,2-ethynyl), with the

41 42 proviso that R and R are selected from other than halo and cyano when directly bonded to N and Z is directly bonded to the quinone ring;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfonyl, and aralkylsulfonylalkyl; Q is formula (II):

.1 l Λ J2 . „1 wherein D , D , J ,, J J i and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more than one can be a covalent bond, no more than one of D ^■W , D , J . ,J J². and K

1 2 1 2 1 1 2 can be O, no more than one of D , D , J , J and K can be S, one of D , D ,

1 1 1 2 1 2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 2 1

O and S, and no more than four of D , D , J , J and K can be N, with the

3 4 3 4 wherein D , D , J , and J are independently selected from the group

3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J can be O,

3 4 3 4 1 no more than one of D , D , J , and J can be S, and no more than three of D ,

2 1 2 9 10 11 12

D , J , and j can be N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

Q can be selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl;

4a_4b K is (CR R )_n wherein n is an integer selected from 1 through 2; 4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, and cyanoalkyl;

4a 4b

R and R , when bonded to the same carbon, can be taken together to form a group selected from the group consisting of oxo, and a linear spacer moiety having from 2 through 7 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkyl ring having 3 through 8 contiguous members, a cycloalkenyl ring having 5 through 8 contiguous members, and a heterocyclyl ring having 5 through 8 contiguous members; E is E , when K is (CR R )_n, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), OC(O)N(R⁷),

(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R^?), (R⁷)NC(O)S,

OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R^?), (R^?)NC(O)N(R⁸),

N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂,

S(O)₂N(R⁷)C(O), C(O)N(R^?)S(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸),

P(O)(R )N(R ), N(R ), ON(R ), CR ^a=CR , ethynylidene (C≡C; 1,2-

4a 4b ethynyl), and C=CR R ;

14 K can be (CH(R )) -T wherein j is selected from a integer from 0 through 2 and T is selected from the group consisting of single covalent bond,

7 14

O, S, and N(R ) with the proviso that (CH(R ))j is bonded to the quinone πng; o 2 14 2

E is E , when K is (CH(R ));-T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R^?)NC(S), (R⁷)NC(O)O,

(R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, P(O)(R⁸),

N(R^?)P(O)(R⁸), P(O)(R⁸)N(R⁷), and N(R^?);

15 K can be G-(CH(R ) wherein k is selected from an integer from 1

7 through 2 and G is selected from the group consisting of O, S, and N(R ) with

15 the proviso that R is other than hydroxy, cyano, halo, ammo, alkylamino, dialkylamino, and sulfhydryl when k is 1;

E is E when K is G-(CH(R ))_jc wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R⁷)NC(O), C(S)N(R⁷), (R^?)NC(S),

OC(O)N(R^?), (R^?)NC(O)O, SC(S)N(R^?), (R^?)NC(S)S, SC(O)N(R^?),

(R⁷)NC(0)S, OC(S)N(R⁷), (R^?)NC(S)O, N(R⁸)C(O)N(R^?),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R^?), N(R⁷)S(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸), P(O)(R⁸)N(R^?),

7 7 4a 4b N(R ), ON(R ), CR =CR , ethynylidene (C≡C; 1,2-ethynyl), and

4a_4b C=CR Tl ;

Y° is formula (IV):

2 than one can be a covalent bond, K is independently selected from the group

+ 5 6 5 6 consisting of C, and N , no more than one of D , D , J , and J can be O, no

more than one of D , D , J , and J can be S, one of D , D , J , and J must

be a covalent bond when two of D , D , J , and J are O and S, no more than

three of D , D , J , and J can be N when K is N , and no more than four of

£ L E £. 1

D , D , J , and J can be N when K is carbon with the provisos that R ,

17 18 19

1 17

R and R can be independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl; b 20 21 ₊ 20 21 22

20 aminoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R can be hydroxy, alkoxy, alkylamino, ammo, and dialkylamino

20 21 22 and that R , R , and R must be other than be hydroxy, alkoxy,

2 + alkylamino, amino, and dialkylamino when K is N ; 20 21 20 22 21 22

20 21 20 22 21 , 22 group consisting of spacer pairs R and R , R and R , and R and R can be used at the same time;

Q can be selected from the group consisting of

N(R²⁶)SO₂N(R²³)(R²⁴), N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵,

N(R )C(S)OR and N(R )C(S)SR with the proviso that no more than one

23 24 26 of R , R , and R can be hydroxy, alkoxy, alkylamino, ammo, or

23 24 26 dialkylamino when two of the group consisting of R , R , and R are bonded to the same atom;

Q can be selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23 24 tiialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),

25 5 23 24 23 24

C(NR )SR , C(O)NR R , and C(O)NR R with the provisos that no

23 24 26 more than one of R , R , andR can be hydroxy, alkoxy, alkylamino,

23 24 26 amino, or dialkylamino when two of the group consisting of R , R , and R

are bonded to the same atom and that said Q group is bonded directly to a carbon atom; 23 24 25 26

23 24

Q is selected from the group consisting of a single covalent bond, n Q

(CR R )tø-( W )_az wherein az is an integer selected from 0 through 1 , b is an integer selected from 1 through 4, and W is selected from the group consisting ofO, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

14 14 14 14 14

(R )NC(O), C(S)N(R ),(R )NC(S), OC(O)N(R ),SC(S)N(R ),

14 14 15 14 14 15 SC(O)N(R ),OC(S)N(R ),N(R )C(O)N(R ),(R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ),(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, P(O)(R⁸),N(R^?)P(O)(R⁸), P(O)(R⁸)N(R^?),N(R¹⁴),

14 14 1 15 ON(R ), (CH(R ))_C-W -(CH(R ))_d wherein c and d are integers

independently selected from 1 through 4, and W is selected from the group

consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

14 14 14 14 14

(R )NC(O), C(S)N(R ),(R )NC(S), OC(O)N(R ),(R )NC(O)O,

14 14 14 14 14

SC(S)N(R ),(R )NC(S)S, SC(O)N(R ),(R )NC(O)S, OC(S)N(R ),

14 15 14 14 15 (R )NC(S)O,N(R )C(O)N(R ),(R )NC(O)N(R ),

1 14 14 15 14

N(R )C(S)N(R ),(R^)NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 8 7 8 8 7 14

N(R )S(O)₂,P(O)(R ),N(R)P(O)(R ),P(O)(R )N(R ),N(R ),

14 14 2 15

ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein e and h are integers independently selected from 0 through 2 and W^ is selected from the group

4a 4b 4a 4b consisting of CR =CR , ethynylidene (O≡C; 1,2-ethynyl), and C=CR R

14 15 with the provisos that R and R are selected from other than halo and cyano

37 38 14 14 when directly bonded to N and that (CR R ) , (CH(R ))_C, (CH(R ))_e and are bonded to E ;

0 go ge

Y can be Q -Q wherein Q is selected from the group consisting of

37 38 14

(CR R )f wherein f is an integer selected from 1 through 6, (CH(R ))_c-

1 15

W -(CH(R ))₍i wherein c and d are integers independently selected from 1

14 14 14 14 14

C(O)N(R ), (R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ),

14 14 14 14 14

(R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S,

14 14 15 14 14 15

OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 8 7 8 8 7 14 N(R )S(O)₂, P(O)(R ), N(R )P(O)(R ), P(O)(R )N(R ), N(R ),

14 14 2 15

ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein e and h are integers

independently selected from 0 through 2 and W^ is selected from the group

4a 4b 4a 4b consisting of CR =CR , ethynylidene (C≡C; 1,2-ethynyl), and C=CR R

37 38 15 when directly bonded to N and that (CR R )f, (CH(R ))_c, and

(CH(R ))_e are bonded to E°; 0 D S*5S *?^S o

Y can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 13-cyclopentyl, 2,3- morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morρholinyl, 3,4- moφholinyl, 3, morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piρeridinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3^-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3- pyπolidinyl, 23-pyrrolidinyl, 2,4-pyπolidinyl, 2,5-pyπolidinyl, 3 ,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-ρyranyl, 4H-2,4- pyranyl, 4H-2,5-ρyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H- ρyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahy dropyranyl, 3 ,4-

38 tetrahydropyranyl, and 3 ,5-tetrahydropyranyl with the proviso that (CH(R ))_r

is bonded to E and Q is bonded to lowest numbered substituent position of

each W ;

Y ean be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

4 selected from 1 through 3, and W is selected from the group consisting of 1,2- cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyI, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-moφholinyl, 2,6- morpholinyl, 3,4-moφholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 13-ρiρerazinyl, 1,4-piρerazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1 ,3-ρiρeridinyl, 1 ,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2, piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyι olidinyl, 23-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyπolidinyl, 3,4- pyrrolidinyl, 2H-23-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-ρyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-ohe-3,4-yl, 2H-pyran-2-one-4,5- yl, 4H-pyran-4-one-23-yl, 2,3-tetrahydrofuranyl, 2,4-teιrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4- 38 tetrahydropyranyl, and 3 ,5-tetrahy dropyranyl with the provisos that (CH(R ))_r

is bonded to E and Q is bonded to highest number substituent position of

4 eachW ;

i can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W^*^ is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl , 2,5-benzothioρhenyl , 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothioρhenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

Cr on

W and that (CH(R ))_r is bonded to E°; JΩ b ssssr SSSSΓ O Ό

Y can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naρhthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2, quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinohnyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,Scinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E°.

In another embodiment of compounds of Formula I or a pharmaceutically acceptable salt thereof, B is formula (V):

.1 J ^ ,„1 wherein D , D , J ₉, J J < and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more l 2 I l than one can be a covalent bond, no more than one of D , D , J , J and K

1 2 1 2 1 1 2 can be O, no more than one of D , D ,J , J andK can be S, one of D ,D , and ¹ nrnstbeacovalentbondwhentwoof ndK¹ a*

1 2 1 2 1

O and S, and no more than four of D , D ,J , J andK can be N;

32 33 34 35 36 b

R ,R ,R ,R ,andR can independently be Q ; π9 10 11 12 13 16 17 „18 19 „32 33 34 35 _J R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,and

36 R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylammo, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfmylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfmylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl ;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R3₂, R3 , R34, R35, and R36;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5- C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R13, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with RJQ, a ring carbon or nitrogen atom adjacent to the RJJ position and two atoms

from the point of attachment may be substituted with R , a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_{j j} , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j2 position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R and R33 positions may be

substituted with R34;

A is selected from the group consisting of single covalent bond,

7 15 15 7 (W ^-(CH R ))_pa and (CH(R ))_pa-(W )_n wherein rr is an integer

C(O)N(R⁷), C(S)N(R^?), (R^?)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R^?),

(R⁷)NS(O)₂, C(NR⁷)N(R⁷), (R⁷)NC(NR^?), and N(R^?);

7 8 R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

„14 15 37 38 . , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl; Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

39 40 S(O), S(O)₂, and CR R ;

R is selected from the group consisting of hydrido, alkyl, and alkoxy; 39 40

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;

0

X and R can be independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylammo, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono; o . 41 42

Z is selected from the group consisting of covalent single bond, (CR R )_q

41 o wherein q is an integer selected from 1 through 2, (CH(R ))_g-W -

42 (CH(R ))p wherein g and p are integers independently selected from 0 through 2 and W is selected from the group consisting of O, S, C(O), C(S),

41 41 41 C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ), (R )NC(O), C(S)N(R ),

41 41 41 41 41

(R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ), (R )NC(S)S,

41 41 41 41

SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

42 41 41 42 42 41

N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ),

41 42 41 41 41

(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R *), N(R )S(O)₂, N(R ),

41 41 2 42 ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein e and h are integers

independently selected from 0 through 2 and W^ is selected from the group

41 42 41 42 consisting of CR =CR , CR R =C; vinylidene), and ethynylidene (C≡C;

41 42

1,2-ethynyl), with the proviso that R and R are selected from other than halo and cyano when directly bonded to N and Z is directly bonded to the quinone ring; 41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, and heteroaralkyl; Q is formula (II):

1 2 1 2 1 than one can be a covalent bond, no more than one of D , D , J , i and K

1 2 1 JL 1 1 2 can be O, no more than one of D , D , J , J and K can be S, one of D , D ,

1 2 1 1 2 1 2 1

J , and K must be a covalent bond when two of D , D , J , 3 and K are

1 2 1 2 1

O and S, and no more than four of D , D , J , J and K can be N, with the

9 10 11 12 13 proviso that R , R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

Q can be selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, saturated heterocyclyl, alkyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl;

4a 4b K is (CR R )_n wherein n is the integer 1 ;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, hydroxyalkyl, alkyl, alkoxyalkyl, and haloalkyl; o 1 4a 4b 1

C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), OC(O)N(R^?),

(R⁷)NC(O)O, SC(S)N(R^?), (R⁷)NC(S)S, SC(O)N(R^?), (R^?)NC(O)S,

OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R^?), (R^?)NC(O)N(R⁸),

N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, ethynylidene (C≡C; 1,2-ethynyl), and C=CR^4&R^4b;

14 K can be (CH(R )) ;-T wherein j is selected from a integer from 0 through 1 and T is selected from the group consisting of single covalent bond,

7 14

O, S, and N(R ) with the proviso that (CH(R )) is bonded to the quinone πng;

E is E , when K is (CH(R ));-T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R⁷), (R^?)NC(S), (R⁷)NC(O)O,

(R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R^?), N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, and N(R⁷); K can be G-(CH(R ))ι, wherein k is the integer 1 and G is selected

7 from the group consisting of O, S, and N(R );

E is E when K is G-(CH(R wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S),

OC(O)N(R⁷), (R^?)NC(O)O, SC(S)N(R^?), (R^?)NC(S)S, SC(O)N(R⁷),

(R⁷)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R^?),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R^?)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R ), N(R )S(O)₂, N(R ), ON(R ), CR =CR , ethynylidene {C≡C;

4a 4b l,2-ethynyl), and C=CR R ;

Y° is formula (IV):

5 6 5 f> wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one can be a covalent bond, K is independently selected from the group

more than one of D , D , J , andJ can be S, one of D , D , J , and J must

be a covalent bond when two of D , D , J , and J are O and S, no more than

three of D , is N , and no more than four of D , D , J , and J can be N when K is carbon with the provisos that R ,

17 18 19

R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; b 20 21 ₊ 20 21 22 Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 ammoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22 R , and R can be hydroxy, alkoxy, alkylamino, amino, and dialkylamino

20 21 22 and that R , R , and R must be other than be hydroxy, alkoxy,

2 + alkylamino, ammo, and dialkylamino when K is N ;

Q can be selected from the group consisting of

N(R )SO₂N(R )(R ), N(R )C(O)OR , N(R )C(O)SR , C(S)SR with the proviso that no more than one

23 24 26 of R , R , andR can be hydroxy, alkoxy, alkylamino, amino, or

Q can be selected from the group consisting of dialkylsulfonium,

trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,

25 5 23 24 23 24

C(NR )SR , C(O)NR R , and C(O)NR R with the provisos that no O^Q 94 96 more than one of R , R , and R can be hydroxy, alkoxy, alkylamino,

23 24 25 26 R , R , R , an R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl; s Q is selected from the group consisting of a single covalent bond,

(CR R ) -(W )_az wherein az is an integer selected from 0 through 1, b is an integer selected from 1 through 2, and W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

(R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), SC(S)N(R¹⁴),

14 14 15 14 14 15

SC(O)N(R ), OC(S)N(R ), N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 14 14 14 1 15 N(R )S(O)₂, N(R ), ON(R ), and (CH(R ))_C-W -(CH(R ))_d wherein

c and d are integers independently selected from 1 through 2, and W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,

14 14 14 14 14

C(S)S, C(O)N(R ), (R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ),

14 14 14 14 14

(R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S,

14 14 15 14 14 15 OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14 N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 14 14 14 2 15

N(R )S(O)₂, N(R ), ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein

e and h are integers independently selected from 0 through 2 and ~w is 4a 4b selected from the group consisting of CR =CR , ethynylidene (C≡C; 1,2-

4a 4b 14 15 ethynyl), and C=CR R with the provisos that R and R are selected from other than halo and cyano when directly bonded to N and that τ on Λ A ^*! Λ

(CR R )_b, (CH(R ))_c, (CH(R ))_e and are bonded to E°;

J0 b ss ss Y can be Q -Q wherein Q is selected from the group consisting of

37 38 14

(CR R )f wherein f is an integer selected from 1 through 4, (CH(R ))_c-

W -(CH(R ))d wherein c and d are integers independently selected from 1

1 1 through 2, and W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R )NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),

14 14 14 14 14

(R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S,

14 14 15 14 14 15

OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, N(R¹⁴), ON(R¹⁴), and (CH(R¹⁴))_e-W²-(CH(R¹⁵))_h wherein

e and h are integers independently selected from 0 through 2 and W^ is

4a 4b selected from the group consisting of CR =CR , ethynylidene (C≡C; 1,2-

4a 4b 14 15 ethynyl), and C=CR R with the provisos that R and R are selected

37 38 from other than halo when directly bonded to N and that (CR R )f ,

(CH(R ))_c, and (CH(R ))_e are bonded to E°; )_r- W , r is an integer

selected from 1 through 2, and W^{"^} is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3- moφholinyl, 2,4-moφholinyl, 2,5-moφholinyl, 2,6-moφholinyl, 3,4- moφholinyl, 3,5-moφholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3- pyπolidinyl, 23-pyrrolidinyl, 2,4-pyπolidinyl, 2,5-pyπolidinyl, 3,4-pyπolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-ρyranyl, 4H-2,3-pyranyl, 4H-2,4- pyranyl, 4H-2,5-ρyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H- pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydroρyranyl, 2,6-tetrahydropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the proviso that (CH(R ))_r

is bonded to E and Q is bonded to lowest numbered substituent position of

each W³;

38.

Y can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

4 selected from 1 through 2, and W is selected from the group consisting of 1 ,2- cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-moφholinyl, 2,4-moφholinyl, 2,5-moφholinyl, 2,6- moφholinyl, 3,4-moφhoIinyl, 3,5-moφhoIinyl, 1,2-ρiperazinyl, 1,3-ρiρerazinyl, 1,4-piperazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1 -piperidinyl, 1,4-piperidinyl, 2,3-ρiperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3-pyrrolidinyl, 2,3-ρyπolidinyl, 2,4-ρyrrolidinyl, 2,5-pyrrolidinyl, 3,4- pyπolidinyl, 2H-2,3-pyranyl, 2H-2,4-ρyranyl, 2H-2,5-ρyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5- yl, 4H-pyran-4-one-23-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahy dropyranyl, 2,4- tetrahydropyranyl, 2_»5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the provisos that (CH(R ))_r

is bonded to E and Q is bonded to highest number substituent position of

4 each W ; Y can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and .w W^{5^} is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W and that (CH(R ))_r is bonded to E°

38 .β can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

6 selected from 1 through 2, and W is selected from the group consisting of 1,4- indenyl, 1 ,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3 ,4-indenyl, 3 ,5-indenyl, 3 ,6-indenyl, 3 ,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,Sindolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyI, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyi, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl,3,4- isoquinolinyl, 3 ,5-isoquinolinyl, 3 ,6-isoquinolinyl, 3 ,7-isoquinolinyl, 3 ,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E°.

In a prefeπed embodiment of compounds of Formula I or a pharmaceutically acceptable salt thereof, B is formula (V):

whe_rei„ D¹. D² Λ J² and K¹ a.e indepe denly se.ec.ed fan «. ^ consisting of C, N, O, S and a covalent bond with the provisos that no more 1 2 1 ; 1 than one can be a covalent bond, no more than one of D , D , J , J and K

1 1 1 2 1 2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 2 1

O and S, and no more than four of D , D , J , J and K can be N;

32 33 34 35 36 b R , R , R , R , andR can independently be Q ;

9 „10 1 1 12 13 32 33 34 35 , 36 R , R , R , R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, alkenyloxy, alkenyloxyalky, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R3 , R33, R34, R35, and R3 ;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5- C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R13, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with RJQ, a ring carbon or nitrogen atom adjacent to the R^ position and two atoms

from the point of attachment may be substituted with R ₂, a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the Rχo

position may be substituted with R_{j j} , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R ₂ position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_j and R33 positions may be

substituted with R34; A is selected from the group consisting of single covalent bond,

(W⁷)_rr-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W⁷)_rr wherein rr is an integer

C(O)N(R⁷), C(S)N(R⁷), (R^?)NC(O), (R⁷)NC(S), S(O), S{0)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, C(NR⁷)N(R^?), (R^?)NC(NR⁷), and N(R^?);

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; Ψ is NH;

X is hydrido;

9 0

R is selected from the group consisting of Z -Q, hydrido, alkyl, alkenyl, and halo;

Z is a covalent single bond; Q is formula (II):

1 2 1 ; 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 1 9 1 than one can be a covalent bond, no more than one of D , D , J , J and K

1 2 1 1 2 1 2 1

J , J and K must be a covalent bond when two of D , D , J , J and K are

1 2 1 2 1

O and S, and no more than four of D , D , J , J and K can be N, with the

4a 4b K is CR R ;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, alkyl, and haloalkyl; E is E , when K is CR R , wherein E is selected from the group consisting of a covalent single bond, (O)N(H), (H)NC(O), C(S)N(H),

(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

14 K can be (CH(R )) j-T wherein j is selected from an integer from 0 through 1 and T is selected from the group consisting of single covalent bond

7 14 and N(R ) with the proviso that (CH(R )); is bonded to the quinone ring

>j ₀ 2 14 2

E is E , when K is (CH(R ));-T, wherein E is selected from the

group consisting of C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

14 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

Y° is formula (IV):

wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one can be a covalent bond, K is independently selected from the group

more than one of D , D , J , and J can be S, one of D , D , J , and J must

5 6 5 6 be a covalent bond when two of D , D , J , and J are O and S, no more than

three of D , D , J , and J can be N when K is N , and no more than four of

D

17 18 19

16 17 18 19 . _{Λ J} , ,

R , R , R , an R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, carboalkoxyaikyl, and cyano; b 20 21 ₊ 20 21 22 Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 aminoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22 R , and R can be hydroxy, alkoxy, alkylamino, ammo, and dialkylamino

20 21 22 and that R , R , and R must be other than be hydroxy, alkoxy,

2 + alkylamino, amino, and dialkylamino when K is N ;

Q can be N(R )SO₂N(R )(R ) with the proviso that no more than

23 24 26 one of R , R , and R can be hydroxy, alkoxy, alkylamino, ammo, or

d ji.a «lkyl ,ami •no w _*hen two o .f, t ,he group consi -sti .ng o _^f RT 23 , R „24 , and R 26 are bonded to the same atom;

Q can be selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23 24 trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴),

26 26 25 23 24 26 26 23 24

N(R °)N(R )C(NR °)N(R )(R ), N(R )N(R^Z°)SO₂N(R^)(R ), ^ 94 9^ 94

C(O)NR R , and C(O)NR R with the provisos that no more than one of

23 24 26

R , R , and R can be hydroxy, alkoxy, alkylamino, ammo, or

23 24 26 dialkylamino when two of the group consisting of R , R , and R are b bonded to the same atom and that said Q group is bonded directly to a carbon atom;

23 24 25 26

S

Q is selected from the group consisting of a single covalent bond and n'-r OO _Λ

(CR R )b"( )_az wherein az is an integer selected from 0 through 1 , b is an integer selected from 1 through 2, and W is selected from the group consisting

14 14 14 of O, S, C(O), S(O)₂, N(R ), and ON(R ) with the proviso that R is

selected from other than halo when directly bonded to N and that (CR R is bonded to E ;

37 ^R

R and R are independently selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

Y can be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and W~^{^} is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naρhthyl, l,Snaphthyl, 1,6-naphthyl, 1,7-naρhthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,Squinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W and that (CH(R ))_r is bonded to E ;

Y ean be Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and W is selected from the group consisting of 1,4- indenyl, 1 ,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3 ^-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyi, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,

2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnoIinyl with the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E .

In a more prefeπed embodiment of compounds of Formula I or a pharmaceutically acceptable salt thereof,

B is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment may be substituted by

32 R , the other carbon adjacent to the carbon at the point of attachment may be

36 32 substituted by R , a carbon adjacent to R and two atoms from the carbon at

33 36 the point of attachment may be substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment may be substituted by

35 33 35 34

R , and any carbon adjacent to both R and R may be substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylsulfϊnyl, alkylsulfonyl, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy, carboxamido, and cyano;

32 33 34 35 36 b

R , R , R , R , and R can independently be Q ; B can be selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R₃₂, R33, R34, R35, and R 6; B can be selected from the group consisting of C3-C10 cycloalkyl, C5-

C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R or R^, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with Rχθ, a ring carbon or nitrogen atom adjacent to the R_j3 position and two atoms

from the point of attachment may be substituted with Rχ₂, a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RIQ

position may be substituted with R_{j j}, a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the Rχ position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy, carboxamido, and cyano;

A is selected from the group consisting of single covalent bond,

(W⁷)_rr-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W⁷)_rr wherein π is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, and C(O);

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; Ψ is NH; X is hydrido;

R is Q, wherein Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment 9 may be substituted by R , the other carbon adjacent to the carbon at the point of

13 9 attachment may be substituted by R , a carbon adjacent to R and two atoms

10 from the carbon at the point of attachment may be substituted by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment may

12 10 12 be substituted by R , and any carbon adjacent to both R and R may be

substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of halo and hydrido; o 1 4a 4b 1

E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, (O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

14 K can be (CH(R )) -T wherein j is selected from an integer from 0 through 1 and T is selected from the group consisting of single covalent bond

7 14 and N(R ) with the proviso that (CH(R ))j is bonded to the quinone ring;

7 R is selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

14 R is selected from the group consisting of hydrido and halo; o 2 14 2

E is E , when K is (CH(R ));-T, wherein E is selected from the

group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; Y is formula (IV):

2 than one can be a covalent bond, K is independently selected from the group

+ 5 6 5 6 consisting of C, and N , no more than one of D , D , J , and J is O, no more

5 6 5 6 5 6 5 6 than one of D , D , J , and J is S, one of D , D , J , and J must be a

covalent bond when two of are O and S, no more than three

5 6 5 6 2 + 5 of D , D , J , and J can be N when K is N , and no more than four of D ,

_ 6 _τ5 _τ6 , .. , „2 . . . _τ>16 _,17 D , J , and j can be N when K is carbon with the provisos that R , R ,

18 19

R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; n \6 _nY7 „18 , 19 . , , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, carboalkoxyaikyl, and cyano; b 20 21 ₊ 20 21 22 Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino 20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,

20 aminoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R can be hydroxy, alkoxy, alkylamino, ammo, and dialkylamino

20 21 22 and that R , R , and R must be other than be hydroxy, alkoxy,

2 + alkylamino, ammo, and dialkylamino when K is N ;

Q can be selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23 24 trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with

23 24 26 the provisos that no more than one of R , R , and R can be hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the group consisting

. -.23 _ 24 „ 6 _^b of R , R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

23 24 25 26 R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl; g

Q is selected from the group consisting of a single covalent bond and

(CR R )b"(W )_az wherein az is an integer selected from 0 through 1, b is the integer 1, and W is selected from the group consisting of O, S, and C(O) with the proviso that (CR R )^ is bonded to E ;

37 38

R and R are independently selected from the group consisting of hydrido, halo, alkyl, and haloalkyl. In a specific embodiment of Formula I, compounds have the Formula

I-S:

or a pharmaceutically acceptable salt thereof, wherein; B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-ρyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, l,2,4-ιriazol-3-yl, 1,2,4-triazol- yl, l,2,4-oxadiazol-3-yl, 1,2,4- oxadiazol-5-yl, 13,4-oxadiazol-3-yl, 13,4-oxadiazoI-5-yl,3-isothiazolyl, 5- isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3- pyridazinyl, 4-pyridazinyl, l,2,4-triazin-3-yl, l,2,4-triazin-5-yl, l,2,4-triazin-6-yl, and l,2,3-triazin-4-yl, wherein a carbon adjacent to the carbon

32 at the point of attachment may be substituted by R , the other carbon adjacent

to the carbon at the point of attachment may be substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment may

33 . 36 be substituted by R , a carbon adjacent to R and two atoms from the carbon

35 at the point of attachment may be substituted by R , and any carbon adjacent

33 35 34 to both R and R may be substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3 β - pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, cyano, and Q ;

B can be selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, isobutyl, 2- methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3- pentynyl, 2-pentyl, l-methyl-2-butenyl, l-methyl-3-butenyl, l-methyl-2- butynyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2- methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3- methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2- hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3- pentenyl, l-methyl-4-pentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3- hexyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, l-propyl-2-propenyl, l-ethyl-2- butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2- heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, l-methyl-2-hexenyl, 1- methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-5-hexenyl, l-methyl-2- hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-4-pentenyl, l-butyl-2-propenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl, 1- methyl-2-heptenyl, l-methyl-3-heptenyl, l-methyl-4-heptenyl, l-methyl-5- heptenyl, l-methyl-6-heρtenyl, l-methyl-2-heptynyl, l-methyl-3-heptynyl, 1- methyl-4-heptenyl, l-methyl-5-heptenyl, l-methyl-6-heptenyl, l-methyl-2- heptenyl, l-methyl-3-heptynyl, l-methyl-4-heptynyl, l-methyl-5-heptynyl, 3- octyl, l-ethyl-2-hexenyl, l-ethyl-3-hexenyl, l-ethyl-4-hexenyl, l-ethyl-2- hexynyl, l-ethyl-3-hexynyl, l-ethyl-4-hexynyl, l-ethyl-5-hexenyl, l-pentyl-2- propenyl, 4-octyl, l-propyl-2-pentenyl, l-propyl-3-pentenyl, l-propyl-4- pentenyl, l-butyl-2-butenyl, l-proρyl-2-ρentynyl, l-propyl-3-pentynyl, 1-butyl- 2-butynyl, l-butyl-3-butenyl, 2,2-difluoroρropyl, 4-trifluoromethyl-5,5,5- trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-penιafiuorohexyl, and 3 - trifluoropropyl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to

A with one or more of the group consisting of R ₂, R33, R34, R35, and R^6',

B can be selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4- methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3- trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4- trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3- trifiuoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1jheptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl, cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl, cyclooct-4-enyl, 2-moφholinyl, 3- moφholinyl, 4-moφholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2- piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyπolidinyl, 3- pyπolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-4-pyranyl, 4H-2- pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 2H-pyran-2-one-3-yl, 2H-pyran-2-one- 4-yl, 2H-pyran-2-one-5-yl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2- tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3- tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3- tetrahydrothienyl, wherein each ring carbon may be optionally substituted with

R33, a ring carbon and nitrogen atoms adjacent to the carbon atom at the point

of attachment may be optionally substituted with R9 or R13, a ring carbon or

nitrogen atom adjacent to the R9 position and two atoms from the point of

attachment may be substituted with Rχø, and a ring carbon or nitrogen atom

adjacent to the R^ position and two atoms from the point of attachment may

be substituted with R_j2;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, dimethylsulfonium, methylethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, butoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- dimethylarnino, N-methylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl, N,N- dimethylamidosulfonyl, acetyl, propanoyl, butanoyl, trifluoroacetyl, pentafiuoropropanoyl, hydroxymethyl, 1 -hydroxy ethyl, 2-hydroxy ethyl, 2,2,2- trifluoro- 1-hydroxyethyl, 2,2,2-trifluoro- 1-trifluoromethyl- 1 -hydroxy ethyl, carboxymethyl, 2-carboxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O,

C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), C(O)CCH₃,

C(O)CCF₃ , CH₂C(O), (O)CCH₂, CH₂CH₂, CH₂CH₂CH₂, CH₃CCH₂,

CF₃CCH₂, CH₃CC(O)CH₂, CF₃CC(O)CH₂, CH₂C(O)CCH₃,

CH₂C(O)CCF₃, CH₂CH₂C(O), and CH₂(O)CCH₂;

2

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-ρyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, l,2,4-triazol-3-yl, l,2,4-triazol-5-yl, l,2,4-oxadiazol-3-yl, 1,2,4- oxadiazol-5-yl, 13,4-oxadiazol-3-yl, 13,4-oxadiazol-5-yl, 3-isothiazolyl, 5- isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3- pyridazinyl, 4-pyridazinyl, 13,5-triazin-2-yl, l,2,4-triazin-3-yl, l,2,4-triazin-5-yl, l,2,4-triazin-6-yl, and l,2,3-triazin-4-yl, wherein a carbon adjacent to the carbon

9 at the point of attachment may be substituted by R , the other carbon adjacent

13 to the carbon at the point of attachment may be substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment may be

10 13 substituted by R , a carbon adjacent to R and two atoms from the carbon at

12 the point of attachment may be substituted by R , and any carbon adjacent to

10 12 11 both R and R may be substituted by R ;

4a 4b . 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido; E is E , when K is CR R , wherein E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be N(H) and CH₂N(H);

E is E , when K is N(H) and CH N(H), wherein E is selected from the group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; i is selected from the group of formulas consisting of:

16 17 18 19 R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifiuoroethyl, 2,2,333- pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, and cyano; Q is selected, when bonded to a carbon, from the group consisting of

20 21 20 21 22

NR R , NR R R , dimethylsulfonium, methylethylsulfonium,

25 23 24 diethylsulfonium, trimethylphosphonium, C(NR )NR R ,

N(R²⁶)C(NR²⁵)N( ²³)(R²⁴), C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

23 24 23 24

C(O)NR R , and C(O)NR R with the provisos that no more than one of

20 21 22

R , R , and R can be hydroxy, methoxy, ethoxy, N-methylammo, N,N- dimethylamino, and N,N,N-trimethylamino, and amino and that no more than one of R , R , andR can be hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino when two of the group consisting of R , R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy, methoxy, ethoxy, isopropoxy, propoxy, 2-aminoethyl, 2-(N-methylamino)ethyl, 2- (N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl, N-(2- hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2- aminoethyl)amino, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N- diethyla ino, and N,N,N-trimethylamino; Q is selected, when bonded to a nitrogen, from the group consisting of oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N- dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino, N-methoxyamino, N- methylamino, N,N-dimethylamino, and N,N,N-trimethylamino; g Q is selected from the group consisting of a single covalent bond, CH₂,

CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S, CF₃C(H)S, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the s 0 proviso that Q is bonded to E through a carbon atom.

In a more prefeπed specific embodiment of Formula I, compounds have the Formula I-MPS:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 13,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

32 the point of attachment may be substituted by R , the other carbon adjacent to

the carbon at the point of attachment may be substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment may

33 36 be substituted by R , a carbon adjacent to R and two atoms from the carbon

35 at the point of attachment may be substituted by R , and any carbon adjacent

33 35 34 to both R and R may be substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimelhylamino, N-ethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3- pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l -hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, cyano, and Q ;

B can be selected from the group consisting of 1-proρenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1- penty], 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, l-methyl-2-butenyl, 1- methyl-3-butenyl, 3-ρentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2- butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3- butenyl, 2,2-difluoropropyl, 2-trifluoromethyl-333-trifluoropropyl, 1,1,1,2,2,2- hexafluoropropyl, 3,3,3-trifluoroprop-l-yl, and 3,33-trifluoroprop-2-yl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group consisting of R3₂, R33, R34, R35, and ^_f,',

B can be selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring carbon may be optionally substituted with R33, a ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R13, a ring carbon or

nitrogen atom adjacent to the R9 position and two atoms from the point of

attachment may be substituted with R Q, and a ring carbon or nitrogen atom

adjacent to the R^ position and two atoms from the point of attachment may

be substituted with Rχ₂;

_^9 10 11 12 13 . , , , ,

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, arninomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1 -hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O, C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), C

C(O)CCH₃, C(O)CCF₃, CH₂C(O), and (O)CCH₂;

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-ρyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 13,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

9 the point of attachment may be substituted by R , the other carbon adjacent to

13 the carbon at the point of attachment may be substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment may be

12 the point of attachment may be substituted by R , and any carbon adjacent to

10 12 11 both R and R may be substituted by R ; 4b 4a 4b

K is CR wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido; o 1 4a 4b 1 E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; K can be N(H) and CH₂N(H); o 2 2

E is E , when K is N(H) and CH₂N(H), wherein E is selected from

the group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y is selected from the group of formulas consisting of:

R are independently selected from the group consisting of hydrido, amidino, guanidino, methoxy, ethoxy, isopropoxy, methylthio, ethylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2- tetrafluoroethoxy, fiuoro, chloro, bromo, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, methoxy carbonyl, ethoxy carbonyl, and cyano; Q is selected, when bonded to a carbon, from the group consisting of

20 21 ₊ 20 21 22 NR R , NR R R , dimethylsulfonium, methylethylsulfonium,

25 23 24 diethylsulfonium, trimethylphosphonium, C(NR )NR R ,

26 25 23 24 26 25 23 24

N(R )C(NR )N(R )(R ), C(O)N(R )C(NR )N(R )(R ),

23 24 23 24 C(O)NR R , and C(O)NR R with the provisos that no more than one of

20 21 22

R , R , and R can be hydroxy, methoxy, ethoxy, N-methylamino, N,N- dimethylamino, N,N,N-trimethylamino, or amino and that no more than one of

23 24 26

R , R , and R can be hydroxy, methoxy, ethoxy, N-methylamino, N,N- dimethylamino, N,N,N-trimethylamino, or amino when two of the group 23 24 26 b consisting of R , R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom; *

20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2- aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl, 2-(NJN,N- trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino, N,N-dimethylamino, and N,N,N-trimethylamino;

Q is selected, when bonded to a nitrogen, from the group consisting of oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N- dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino, N-methoxyamino, N- methylamino, N,N-dimethylarnino, and NJN,N-trimethylamino; g

Q is selected from the group consisting of a single covalent bond, CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S,

CF₃C(H)S, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the s o proviso that Q is bonded to E through a carbon atom.

In an even more preferred specific embodiment of compounds of Formula I , compounds have the Formula I-EMPS :

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-ρyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, and 4- pyridyl, wherein a carbon adjacent to the carbon at the point of attachment may 32 be substituted by R , the other carbon adjacent to the carbon at the pomt of

attachment may be substituted by R , a carbon adjacent to R and two atoms

33 from the carbon at the point of attachment may be substituted by R , a carbon

36 adjacent to R and two atoms from the carbon at the point of attachment may

35 33 35 be substituted by R , and any carbon adjacent to both R and R may be

34 substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methoxy, ethoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2- aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, trifluoromethyl, pentafiuoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l- hydroxyethyϊ, 2,2,2-trifluoro-l-trifluoromethyl-l-hydroxyethyl, methoxy carbonyl, ethoxycarbonyl, cyano, and Q ; B can be selected from the group consisting of propyl, isopropyl, butyl, sec-butyl, isobutyl, 1-ρentyl, 2-pentyl, 3-ρentyl, 2-methylbutyl, 3-methylbutyl, 2,2-difluoropropyl, 2-trifluoromethyl-3,33-trifluoropropyl, 1,1,1,2,2,2- hexafluoropropyl, 3,33-trifluoroρrop-l-yl, and 333-tπfluoroprop-2-yl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group consisting of R3 , R33, R34, R35, and R3 ;

nitrogen atom adjacent to the R9 position and two atoms from the point of

attachment may be substituted with RJQ, and a ring carbon or nitrogen atom adjacent to the R^ position and two atoms from the point of attachment may

be substituted with Rχ₂;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, carboxy, methoxy, ethoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N- methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano; A is selected from the group consisting of single covalent bond, O,

C{0), CH₂, CH₂C(O), and (O)CCH₂;

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-ρyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 13,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

13 the carbon at the point of attachment may be substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment may be

12 the point of attachment may be substituted by R , and any carbon adjacent to

10 12 11 both R and R may be substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido; o 1 4a 4b 1 E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

E is E , when K is N(H) and CH₂N(H), wherein E is selected from

the group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; is selected from the group of formulas consisting of:

_ 16 _ 17 _ 18 , --.19 . , , , , , - ,

R , R , R , and R are independently selected from the group consisting of hydrido, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, 2,2,2- trifiuoroethyl, trifluoromethoxy, fluoro, chloro, bromo, acetyl, trifluoroacetyl, methoxycarbonyl, ethoxycarbonyl, and cyano;

_^b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , dimethylsulfonium, methylethylsulfonium, diethylsulfonium, trimethylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

20 21 22 the provisos that no more than one of R , R , and R can be hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino,

23 24 26 or amino and that no more than one of R , R , and R can be. hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino,

23 24 26 or amino when two of the group consisting of R , R , and R are bonded

to the same atom and that said Q group is bonded directly to a carbon atom; 20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2- aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl, 2-(N,N,N- trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino, N,N-dimeιhylamino, and N,N,N-trimethylamino; g

Q is selected from the group consisting of a single covalent bond, CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the proviso that Q^s is bonded to E through a carbon atom.

In a pref eπed embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogen with a removable hydrogen or a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to A is optionally substituted by

32 R , a nitrogen with a removable hydrogen or a carbon at the other position adjacent to the point of attachment is optionally substituted by , a nitrogen

32 with a removable hydrogen or a carbon adjacent to R and two atoms from the

33 point of attachment is optionally substituted by R , a nitrogen with a

36 removable hydrogen or a carbon adjacent to R and two atoms from the point

35 of attachment is optionally substituted by R , and a nitrogen with a removable 33 35 hydrogen or a carbon adjacent to both R and R is optionally substituted by

R³⁴;

„9 10 11 12 „13 32 33 34 35 _{J n}36 R , R , R , R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylammo, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy, carboxamido, carboxamidoalkyl, and cyano;

„32 33 „34 35 , 36 . , , , . „ h R , R , R , R , and R are independently optionally Q ; B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A

32 33 34 35 36 with one or more of the group consisting of R , R , R , R , and R ; B is optionally a C3-C12 cycloalkyl or C4-C9 saturated heterocyclyl,

33 wherein each ring carbon is optionally substituted with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon

9 13 atom at the point of attachment are optionally substituted with R or R , a ring

9 carbon or nitrogen atom adjacent to the R position and two atoms from the 10 point of attachment is optionally substituted with R , a ring carbon or nitrogen

13 adjacent to the R position and two atoms from the point of attachment is

12 optionally substituted with R , a ring carbon or nitrogen three atoms from the

10 point of attachment and adjacent to the R position is optionally substituted

11 with R , a ring carbon or nitrogen three atoms from the point of attachment

12 , , 33 and adjacent to the R position is optionally substituted with R , and a ring carbon or nitrogen four atoms from the point of attachment and adjacent to the

11 33 34

R and R positions is optionally substituted with R ;

A is selected from the group consisting of a bond, π 1 ^ 1 ^ π ( W )_rr-(CH(R ))_pa, and (CH(R ))_pa-(W )_π wherein π is 0 or 1 , pa is an

7 integer selected from 0 through 6, and W is selected from the group

consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R^?) with the proviso that no more than one of the group consisting of π and pa is 0 at the same time;

7 R is selected from the group consisting of hydrido, hydroxy, and alkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl;

Ψ is NH or NOH;

X is selected from the group consisting of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q; o 41 42

Z is selected from the group consisting of a bond, (CR R )_q

41 o wherein q is an integer selected from 1 through 3, and (CH(R ))_g-W - 42 (CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O. S, C(O), S(O),

41 41

N(R ), and ON(R );

Z° is optionally (CH(R⁴¹))_e-W²²-(CH(R⁴²))_h wherein e and h are

22 independently 0 or 1 and W is selected from the group consisting of

41 42 CR =CR , 1,2-cycloρropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 13-cyclopentyl, 2,3-moφholinyl, 2,4-moφholinyl, 2,6-moφholinyl, 3,4-moφholinyl, 3,5-moφholinyl, 1,2-piperazinyl, 13-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyπolidinyl, 1,3-pyrrolidinyl, 23-ρyrrolidinyl, 2,4-pyπolidinyl, 2,5-pyrrolidinyl, 3,4-pyπolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,

2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1 ,4-quinone ring and ^'ψ is optionally substituted with one or more

9 10 11 12 13 substituents selected from the group consisting of R , R , R , R , and R ;

41 42

R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogen with a removable hydrogen or a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is optionally substituted by

9 R , a nitrogen with a removable hydrogen or a carbon at the other position

13 adjacent to the point of attachment is optionally substituted by R , a nitrogen

9 with a removable hydrogen or a carbon adjacent to R and two atoms from the

point of attachment is optionally substituted by R , a nitrogen with a

13 removable hydrogen or a carbon adjacent to R and two atoms from the point

12 of attachment is optionally substituted by R , and a nitrogen with a removable hydrogen or a carbon adjacent to both R and R is optionally substituted by

11

R

Q is optionally hydrido with the proviso that Z is selected from other than a bond;

4a 4b K is CR R ;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; o 4a 4b 1 1

E , with the proviso that K is CR R , is E wherein E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and

C(O)N(H)S(O)₂;

14 K is optionally (CH(R )):-T wherein j is 0 or 1 and T is a bond or

7 14

N(R ) with the proviso that (CH(R )); is bonded to the phenyl ring;

14 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl; o 14 2 2

E , with the proviso that K is (CH(R )) -T, is E wherein E is selected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),

(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g contiguous atoms from the point of attachment of Q to said phenyl or said

heteroaryl to said phenyl or said heteroaryl is substituted by Q , a carbon s 17 adjacent to the point of attachment of Q is optionally substituted by R , s another carbon adjacent to the point of attachment of Q is optionally 18 b 16 substituted by R , a carbon adjacent to Q is optionally substituted by R , b 19 and another carbon adjacent to Q is optionally substituted by R ;

16 17 18 19

R , R , R , an R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, and cyano;

R or R is optionally selected from the group consisting of

NR²°R²¹, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the

proviso that R , R , and Q are not simultaneously hydrido;

, 90 91

Q is selected from the group consisting of NR R , aminoalkyl,

hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the

• , , „_n20 21 . , proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time,

23 24 with the further proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

_^20 21 23 A 25 , 26 . , , ,

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, aminoalkyl, amino, dialkylamino, alkylamino, and hydroxyalkyl; s 37 38

Q is selected from the group consisting of a bond, (CR R

14 1 wherein b is an integer selected from 1 through 4, and (CH(R ))_C-W -

15 (CH(R )),_j wherein c and d are integers independently selected from 1

1 14 through 3 and W is selected from the group consisting of C(O)N(R ),

(R^M)NC(O), S(O), S(O)₂, S(O)₂N(R^M), N(R^M)S(O)₂, and N(R^W), with the 14 proviso that R is selected from other than halo when directly bonded to N,

37 38 14 and with the additional proviso that (CR R )^ and (CH(R ))_c are bonded to E ;

37 38

R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl;

38 38

R is optionally aroyl or heteroaroyl, wherein R is optionally substituted with one or more substituents selected from the group consisting of

16 17 „18 19

R , R , R , and R ;

i is optionally Y wherein Y is Q -Q ;

_n h qq qq 14 2 15 is optionally Q -Q wherein Q is (CH(R ))_e-W -(CH(R ))_h,

2 4a 4b wherein e and h are independently 1 or 2 and W is CR =CR , with the

14 o proviso that (CH(R ))_e is bonded to E ;

^0 . . _t1 b „ssss ~b „ssssr , . ._ssss . _r,_{U n}38 Y is optionally Q -Q or Q -Q wherein Q is (CH(R ))_r-

W , Q is (CH(R ))_r-W , r is 1 or 2, W and W are independently selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo( 1 ,2-a)pyridinyl, 3 ,4-imidazo( 1 ,2-a)pyridinyl, 3 ,5-imidazo( 1 ,2-a)py ridinyl , 3 ,6-imidazo( 1 ,2-a)pyridinyl , 3,7-imidazo(l,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, l,Snaphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naρhthyl, 2,6-naρhthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl,

4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7- cinnolinyl, 3,8-cinnolinyl, 4,Scinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8- cinnolinyl, and each carbon and hyrido containing nitrogen member of the ring of the W and of the ring of the W , other than the points of attachment of W~^

and W , is optionally substituted with one or more of the group consisting of

R , R , R , and R , with the proviso that Q is bonded to lowest number w⁵ b . substituent position of each W with the further proviso that Q is bonded to

highest number substituent position of each W , and with the additional

proviso that (CH(R ))_r is bonded to E .

In a more prefeπed embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substituted by R , the other carbon adjacent to the 36 carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

33 36 optionally substituted by R , a carbon adjacent to R and two atoms from the

35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxamido, cyano, and

Q^b;

B is optionally selected from the group consisting of hydrido, tiialkyisilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A

32 33 34 35 36 with one or more of the group consisting of R , R , R , R , and R ;

B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,

9 carbon or nitrogen atom adjacent to the R position and two atoms from the

10 point of attachment is optionally substituted with R , a ring carbon or nitrogen

13 atom adjacent to the R position and two atoms from the point of attachment 12 is optionally substituted with R , a ring carbon or nitrogen atom three atoms

from the point of attachment and adjacent to the R position is optionally

substituted with R , a ring carbon or nitrogen atom three atoms from the

12 point of attachment and adjacent to the R position is optionally substituted

33 with R , and a ring carbon or nitrogen atom four atoms from the point of

11 33 attachment and adjacent to the R and R positions is optionally substituted

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano;

15 7

A is bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1, pa is an integer

7 selected from 0 through 3, and W is selected from the group consisting of O,

S, C(O), (R⁷)NC(O), (R^?)NC(S), and N(R⁷), with the proviso that W^? is bonded to the N(H) on the 1,4-quinone ring;

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q; o 41 42 Z is selected from the group consisting of a bond, (CR R )_q

41 o 42 wherein q is 1 or 2, and (CH(R ))_g-W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and is selected from the

41 41 group consisting of O, S, C(O), S(O), N(R ), and ON(R ); n 41 22 42

Z is optionally (CH(R ))_e-W -(CH(R ))_h wherein e and h are

independently 0 or 1 and W is selected from the group consisting of

41 42 CR =CR , 1,2-cycloproρyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 13-cyclopentyl, 2,3-moφholinyl, 2,4-moφholinyl, 2,6-moφholinyl, 3,4-moφholinyl, 3,5-moφholinyl, 1,2-piperazinyl, 1 -piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, l,2-pyrrolidinyl,l,3-pyπolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,

2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1 ,4-quinone ring and ^~W is optionally substituted with one or more

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and amino;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

Q is optionally hydrido with the proviso that Z is other than a bond;

4a 4b K is CR R ;

4a 4b

R and R are independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; o 4a 4b 1 1

E , with the proviso that K is CR R , is E wherein E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H), and N(H)S(O)₂;

14 K is optionally (CH(R )):-T wherein j is 0 or 1 and T is a bond or

7 14

N(R ) with the proviso that (CH(R )) is bonded to the phenyl ring;

14 R is hydrido or halo; o 14 2 2

E , with the proviso that K is (CH(R )),-T, is E wherein E is selected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),

(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon s of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is optionally substituted by R , and another carbon adjacent to Q is optionally

substituted , by R¹⁹ ;

_^16 17 _^18 19 ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

26 25 23 24 25 23 24

N(R )C(NR )N(R )(R ), and C(NR )NR R , with the proviso that no

20 21 more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time, with the further proviso that

23 24 no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino;

37 3R Q is selected from the group consisting of a bond, (CR R )^

14 1 wherein b is an integer selected from 1 through 4, and (CH(R ))_C-W -

(CH(R ))<_j wherein c and d are integers independently selected from 1

1 14 through 3 and W is selected from the group consisting of C(O)N(R ),

(R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the

14 proviso that R is selected from other than halo when directly bonded to N, "V7 R 37 ^R and with the additional proviso that (CR R )^ and (CR R )^, and

(CH(R¹⁴))_C are bonded to E°;

37 38

38 38

R is optionally aroyl or heteroaroyl, wherein R is optionally substituted with one or more substituents selected from the group consisting of _π16 17 18 _{ι π}19 R , R , R , and R ;

Y is optionally Y wherein Y is Q -Q ;

Y° is optionally Q^b-Q^SS wherein Q^SS is (CH(R¹⁴))_e-W²-(CH(R¹⁵))_h,

_ 4a 4b wherein e and h are independently 1 or 2 and .wW^{2^} : is CR =CR with the

14 o proviso that (CH(R ))_e is bonded to E .

In an even more preferred embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

32 ring to A is optionally substituted by R , the other carbon adjacent to the

carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

33 36 optionally substituted by R , a carbon adjacent to R and two atoms from the 35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R )) _a-(W )_n wherein π is 0 or 1, pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, W -

42 o

(CH(R ))_p wherein p is 0 or 1 and W is selected from the group consisting

of O, S, and N(R⁴¹);

41 42 R and R are independently hydπdo or alkyl;

13 carbon at the point of attachment is optionally substituted by R , a carbon

12 carbon at the point of attachment is optionally substituted by R , and any

carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylaikoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroaryla ino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three

atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ; 16 17 18 1

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

25, 23 24 20 21

C(NR )NR R , with the proviso that no more than one of R and R is

23 hydroxy at the same time and with the further proviso that no more than one of R

24 and R is hydroxy at the same time;

20 21 23 24 25

R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g

Q is selected from the group consisting of a bond, CH₂, and CH CH .

In another even more preferred embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the 32 point of attachment of B to A with one or more of the group consisting of R ,

33 34 35 , „36 R , R , R , and R ;

32 33 34 35 36

R , R , R , R , andR are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1, pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, W -

42 o

(CH(R ))_p wherein p is 0 or 1 and W is selected from the group consisting

of O, S, and N(R⁴¹);

41 42 R and R are independently hydrido or alkyl;

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is 10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

10 12

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

optionally substituted by R , and another carbon adjacent to Q is optionally

substituted by R ; 16 17 18 19

R or R is optionally selected from the group consisting of

20 21 26 25 23 24 25 23 24

NR R ,N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that

20 21 . , , , . „ . , , - no more than one of R and R is hydroxy at the same time and with the

23 24 . further proviso that no more than one of R and R is hydroxy at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; s Q is selected from the group consisting of a bond, CH₂, and

CH CH .

In still another even more prefeπed embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl, wherein

33 each ring carbon is optionally substituted with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point

9 13 of attachment are optionally substituted with R or R , a ring carbon or

9 nitrogen adjacent to the R position and two atoms from the point of attachment

10 13 is optionally substituted with R , a ring carbon or nitrogen adjacent to the R position and two atoms from the point of attachment is optionally substituted

12 with R , a ring carbon or nitrogen three atoms from the point of attachment

and adjacent to the R position is optionally substituted with R , a πng carbon or nitrogen three atoms from the point of attachment and adjacent to the

12 33

R position is optionally substituted with R , and a ring carbon or nitrogen

11 33 four atoms from the point of attachment and adjacent to the R and R

34 positions is optionally substituted with R ;

9 11 13

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano;

33 34

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, and cyano; L

R is optionally Q ;

15 7 A is a bond or (CH(R ))_pa-(W )_rr wherein rr is 0 or 1 , pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl; X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, o 42 o W -(CH(R ))_p wherein p is 0 or 1 and W is selected from the group

41 consisting of O, S, and N(R );

41 42

R and R are independently hydrido or alkyl;

13 carbon at the point of attachment is optionally substituted by R , a carbon

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is optionally substituted by R , an anot er car on a acent to is optionally

substituted by R ;

„16 17 18 19 ,

R¹⁶ or R¹⁹ is optionally NR²°R²¹ or and C(NR²⁵)NR²³R²⁴, with the

16 19 h proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

25 93 24 90 91 C(NR )NR R , with the proviso that no more than one of R and R is

24 and R is hydroxy at the same time;

20 21 23 24 25

R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; S

Q is selected from the group consisting of a bond, CH , and CH₂CH₂.

In an additional even more preferred embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, tiialkyisilyl, C2-C4 alkyl, C3-C5 alkylenyl, C3-C4 alkenyl, C3-C4 alkynyl, and C2-C4 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 3 atoms from the point of attachment of B to A with one or more

32 33 34 of the group consisting of R , R , and R ;

32 33 34

R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, and cyano;

15 7

A is (CH(R ))_pa-N(R ) wherein pa is an integer selected from 0

7 through 2 and R is hydrido or alkyl;

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R² is Z°-Q;

Z is a bond or CH₂;

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

16 b optionally substituted by R , and another carbon adjacent to Q is optionally

substituted by R ;

_^ 16 17 18 19 . , , , ,

R or R is optionally selected from the group consisting of

NR R ,N(R )C(NR )N(R )(R ), and C(NR )NR . R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; 90 91 Q is selected from the group consisting of NR R , hydrido,

C(NR )NR R , and N(R )C(NR )N(R )(R ), with the proviso that

20 21 no more than one of R and R is hydroxy at the same time and with the

23 24 further proviso that no more than one of R and R is hydroxy at the same time;

20 21 23 24 25 26 R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy;

Q is selected from the group consisting of a bond, CH , and

CH₂CH₂. In a fifth even more preferred embodiment of a compound of Formula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substituted by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the

35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carboalkoxy, carboxy, carboxamido, cyano, and Q ; B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A r.³2 „33 34 „35 36 with one or more of the group consisting of R , R , R , R , and R ; B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,

9 carbon or nitrogen adjacent to the R position and two atoms from the point of

attachment is optionally substituted with R , a ring carbon or nitrogen adjacent

13 to the R position and two atoms from the point of attachment is optionally

12 substituted with R , a ring carbon or nitrogen three atoms from the point of

attachment and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent

12 33 to the R position is optionally substituted with R , and a ring carbon or

11 nitrogen four atoms from the point of attachment and adjacent to the R and

33 34 R positions is optionally substituted with R ;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano; 15 7

A is a bond or (CH(R )) _a-(W )_rr wherein π is 0 or 1, pa is an

7 integer selected from 0 through 3, and W is selected from the group

consisting of O, S, C(O), (R^?)NC(O), (R⁷)NC(S), and N(R⁷);

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R² is Z°-Q; o 41 42

Z is selected from the group consisting of a bond, (CR R )_q

41 o 42 wherein q is 1 or 2, and (CH(R ))_g~W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W is selected from the

41 41 group consisting of O, S, C(O), S(O), N(R ), and ON(R ); 1 ylO Z° is optionally (CH(R ))_e-W -(CH(R ))_h wherein e and h are

independently 0 or 1 and W^ is selected from the group consisting of

41 42 CR =CR , 1,2-cycloρropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 13-cyclopentyl, 2,3-moφholinyl, 2,4-moφholinyl, 2,6-moφholinyl, 3,4-moφholinyl, 3,5-moφholinyl, 1,2-piperazinyl, 13-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1 ,3-piperidinyl, 2,3-piperidinyl, 2,4-piρeridinyl, 2,6-piperidinyl, 3,4-piperidinyl, l,2-pyπolidinyl,13-pyπOlidinyl, 2,3-pyπolidinyl, 2,4-pyπolidinyl, 2,5-pyπolidinyl, 3,4-pyπolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,

2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1 ,4-quinone ring and W^ is optionally substituted with one or more

9 10 11 12 13 substituents selected from the group consisting of R , R , R , R , and R ; 41 42

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R , with the proviso that Q is other than a phenyl when Z is a bond;

4a 4a

K is CHR wherein R is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E is selected from the group consisting of a bond, C(O)N(H),

(H)NC(O), (R^?)NS(O)₂, and S(O)₂N(R^?);

Y^AT is Q^b-Q^S;

37 38 Q is (CR R )tø wherein b is an integer selected from 1 through 4,

37 R is selected from the group consisting of hydrido, alkyl, and haloalkyl, and

38 R is selected from the group consisting of hydrido, alkyl, haloalkyl, aroyl, and heteroaroyl with the proviso that there is at least one aroyl or heteroaroyl substituent, with the further proviso that no more than one aroyl or heteroaroyl

37 38 is bonded to (CR R )^ at the same time, with the still further proviso that said aroyl and said heteroaroyl are optionally substituted with one or more 1 -f£ I T 1 Q 1 0 substituents selected from the group consisting of R , R , R , and R , with another further proviso that said aroyl and said heteroaroyl are bonded to the CR R that is directly bonded to E , with still another further proviso

37 38 that no more than one alkyl or one haloalkyl is bonded to a CR^' R at the same time, and with the additional proviso that said alkyl and haloalkyl are bonded to a carbon other than the one bonding said aroyl or said heteroaroyl;

16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; τ R, l⁶ or R¹⁹ i .s opti.ona„lly se,lected, . f,rom the group consi •sti•ng o.f with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21 Q is selected from the group consisting of NR R , hydrido,

26 25 23 24 25 23 24

N(R )C(NR )N(R )(R ), and C(NR )NR R , with the proviso that

20 21 . no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time and with the

23 24 further proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino. In a most preferred embodiment of compounds of Formula I, said compound is the formula:

32 ring to A is optionally substituted by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the

35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein rr is 0 or 1 , pa is an

7 7 integer selected from 0 through 3, and W is N(R );

7 R is hydrido or alkyl;

R² is Z°-Q; Z is a bond;

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano; ϊ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three s atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of s . . 18 b attachment of Q is optionally substituted by R , a carbon adjacent to Q is

optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ;

R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; τ.16 $ . • „ ^²⁰ _^ ²* _ττ,25 _m23 24 . , , R or R is optionally NR R or C(NR )NR R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

C(NR )NR R ;

20 21 23 24 25

R , R , R , R , and R are independently hydrido or alkyl;

Q is CH₂.

In a further most preferred embodiment of compounds of Formula I, said compound is the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the 32 point of attachment of B to A with one or more of the group consisting of R , _π33 34 „35 , 36 R , R , R , and R ;

32 33 34 35 36

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1 , pa is an

7 7 integer selected from 0 through 3, and W is N(R );

7 R is hydrido or alkyl;

R² is Z°-Q;

Z is a bond;

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 . 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ; 9 11 13

10 12 R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano; Ϊ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three s atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

1 f K optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ;

16 _ 17 _ 18 _{1 T},19 . R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, ammoalkyl, and cyano;

R or R is optionally selected from the group consisting of

20 21 26 25 23 24 25 23 24

NR R ,N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

N(R²⁶)C(NR²⁵)N(R²³)(R²⁴\ and C(NR²⁵)NR²³R²⁴; are independently hydrido or alkyl;

Q^S is CH₂.

In a still further most preferred embodiment of compounds of Formula I, said compound is the formula:

9 13 of attachment are optionally substituted with R or R , a ring carbon or

nitrogen adjacent to the R position and two atoms from the point of attachment

12 with R , a ring carbon or nitrogen three atoms from the point of attachment

10 11 and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent to the

12 . 33

R position is optionally substituted with R , and a ring carbon or nitrogen 11 33 four atoms from the point of attachment and adjacent to the R and R

34 positions is optionally substituted with R ;

9 11 13

10 12

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano;

33 34

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, and cyano;

33 h

R is optionally Q ;

15 7

A is a bond or (CH(R )) _a~(W )_rr wherein π is 0 or 1, pa is an

7 7 integer selected from 0 through 3, and W is N(R );

7 R is hydrido or alkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z°-Q;

Z is a bond;

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

Y is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

optionally substituted by R , and another carbon adjacent to Q is optionally

substituted , , by R τ ⁹ ;

_^ 16 17 . 18 19 . , , , , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

16 19 20 21 25 23 24 R or R is optionally NR R or C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydndo, and

25 23 24 C(NR )NR R ; 20 21 23 24 25

R , R ,R , R , and R are independently hydrido or alkyl;

Q is CH₂.

In a prefeπed specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, l,2,4-triazol-3-yl, l,2,4-triazol-5-yl, l,2,4~oxadiazol-3-yl, 1,2,4-oxadiazol- yl, l,3,4-oxadiazol-3-yl, 13,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 13,5-triazin-2-yl, l,2,4-triazin-3-yl, l,2,4-triazin-5-yl, l,2,4-triazin-6-yl, l,2,3-triazin-4-yl, and l,23-triazin-5-yl„ wherein a carbon adjacent to the carbon at the point of attachment is optionally

32 substituted by R , the other carbon adjacent to the carbon at the point of

attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by

33 36

R , a carbon adjacent to R and two atoms from the carbon at the point of

35 attachment is optionally substituted by R , and any carbon adjacent to both

33 35 34

R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, nitro, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl,

2,2,2-trifluoro- 1 -trifluoromethyl- 1 -hydroxyethyl , carboxymethyl, methoxy carbonyl, ethoxy carbonyl, amidocarbonyl, N-methylamidocarbonyl,

N,N-dimethylamidocarbonyl, cyano, and Q ;

B is selected from the group consisting of hydrido, trimethylsilyl, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-ρentyl, l-methyl-2-butenyl, l-methyl-3-butenyl, l-methyl-2-butynyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyI-2-butenyI, 2-methyI-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-4-pentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3-hexyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, l-propyl-2-propenyl, l-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-5-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-4-pentenyl, l-butyl-2-propenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl, l-methyl-2-heptenyl, l-methyl-3-heptenyl, l-methyl-4-heptenyl, l-methyl-5-heptenyl, l-methyl-6-heptenyl, l-methyl-2-heptynyl, l-methyl-3-heptynyl, l-methyl-4-heptenyl, l-methyl-5-heptenyl, l-methyl-6-heptenyl, l-methyl-2-heptenyl, l-methyl-3-heptynyl, l-methyl-4-heptynyl, l-methyl-5-heptynyl, 3-octyl, l-ethyl-2-hexenyl, l-ethyl-3-hexenyl, l-ethyl-4-hexenyl, l-ethyl-2-hexynyl, l-ethyl-3-hexynyl, l-ethyl-4-hexynyl, l-ethyl-5-hexenyl, l-pentyl-2-propenyl, 4-octyl, 1 -propyl -2-pentenyl, l-propyl-3-pentenyl, l-propyl-4-pentenyl, l-butyl-2-butenyl, l-propyl-2-pentynyl, l-propyl-3-pentynyl, l-butyl-2-butynyl, l-butyl-3-butenyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentefluorohexyl, and 333-trifluoropropyl, wherein each member of group B is optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group

_^32 _π33 34 35 , „36 consisting of R , R , R , R , and R ;

B is optionally selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, adamantyl, norbomyl, 3-trifluoromethylnorbornyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicycloβ.1.0]hexan-6-yl, cycloheptyl, cyclooctyl, 2-moφholinyl,

3-moφholinyl, 4-moφholinyl, 1-piperazinyl, 2-piρerazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyπolidinyl, 2-pyπolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-ρyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahy dropyranyl, 3-tetrahydropyranyl,

4-tetrahy dropyranyl, 2-tetrahy drothienyl, and 3-tetrahydrothienyl, wherein each

33 ring carbon is optionally substituted with R , a ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment is optionally

9 13 . 9 substituted with R or R , a ring carbon or nitrogen atom adjacent to the R position and two atoms from the point of attachment is optionally substituted wi .t,h R¹⁰ , and , a π •ng car ,bon or ni •trogen atom ad Λj-acent to t ,he R _n13 posi .ti.on and

12 two atoms from the point of attachment is optionally substituted with R ;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxy methyl, 1 -hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,

N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,

N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy, 4-trifiuoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino,

5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,Sdifluorobenzyloxy, 3,5-difluorophenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluoroρhenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy, 3 ,5-dimethylbenzyloxy , 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulf onyl , 3-trifluoromethoxybenzyloxy , 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyρhenoxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3, 5-bis-trifluoromethyl benzyl oxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluoroρhenoxy, 2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy;

A is selected from the group consisting of a bond, O, S, NH, N(CH3),

N(OH), C(O), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,

C(O)N(CH₃), CF₃CC(O), C(O)CCH₃, C(O)CCF₃, CH₂C(O), (O)CCH₂,

CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, CF₃CHCH₂, CH₃CC(O)CH₂,

CF₃CC(O)CH₂, CH₂C(O)CCH₃, CH₂C(O)CCF₃, CH₂CH₂C(O), and

CH₂(O)CCH₂;

A is optionally selected from the group consisting of CH₂N(CH3),

CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that B is hydrido;

X° is selected from the group consisting of hydrido, hydroxy, amino, thiol, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, methylarnino, dimethylamino, cyano, methyl, ethyl, isopropyl, propyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333- pentafluoropropyl, methoxy, ethoxy, propoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy ethyl, methoxyamino, ethoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafϊuoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q; Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, 0,

S, NH, N(CH₃), CH(OH), OCH₂, SCH₂, N(H)CH₂, CH₂O, CH₂S, CH₂N(H), CH(NH₂), CH₂CH(OH), CH₂CHNH₂, CH(OH)CH₂, and

CH(NH₂)CH₂;

Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-ρyrazolyl, l,2,4-triazol-3-yl, 1,2,4-triazol- yl, l,2,4-oxadiazol-3-yl, 1,2,4- oxadiazol-5-yl, l,3,4-oxadiazol-3-yl, l,3_>4-oxadiazol-5-yl, 3-isothiazolyl, 5- isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, 2-ρyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-ρyrimidinyl, 3- pyridazinyl, 4-pyridazinyl, l,3,5-triazin-2-yl, l,2,4-triazin-3-yl, l,2,4-triazin-5-yl, l,2,4-triazin-6-yl, l,2,3-triazin-4-yl, and l,2,3-triazin-5-yl, wherein a carbon

9 adjacent to the carbon at the point of attachment is optionally substituted by R , the other carbon adjacent to the carbon at the point of attachment is optionally

13 9 substituted by R , a carbon adjacent to R and two atoms from the carbon at

the point of attachment is optionally substituted by R , a carbon adjacent to

13 R and two atoms from the carbon at the point of attachment is optionally

12 10 12 substituted by R , and any carbon adjacent to both R and R is optionally

11 substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of methyl, ethyl, propyl, isopropyl, fluoro, chloro, hydroxy, hydroxymethyl, 1-hydroxyethyl, methoxymethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoromethyl, methylthiomethyl, and hydrido;

E° is a bond, C(O)N(H), (H)NC(O), and S(O)₂N(H);

is selected from the group of formulas consisting of:

> _Λ , ? _n ^ 16 „ 17 _{c n}l8 , 19 -Q -4-Q -2-R -3-R -5-R -6-R benzene,

-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

-Q -6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,

-Q^b-5-Q^S-3-R¹⁶-6-R¹⁸pyrazine,

r > , ^ _{^ τ}.18 _^„18 _Λ 19 ., . -Q -6-Q -2-R -5-R -4-R pyπdazme,

Λb _Λs , 17 _ 18 . -Q -5-Q -4-R -6-R pyπmidme,

b s 16 19 -2-Q -4-R -6-R pyrimidine,

b s 16 19 -5-Q -4-R -2-R thiophene,

-5-Q^S-3 -R -4-R thiophene,

b s 16 19 _5_Q -4-R -2-R furan,

2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷furan,

„ _^b _ _Λs „ 16 _Λ 19

3-Q -5-Q -4-R -2-R pyπole,

b s _r 6 _{Λ n}V7 2-Q -5-Q - -R -4-R pyπole,

4-Q -2-Q -5-R imidazole,

2-Q -4-Q^S-5-R imidazole,

_^h _{^ Λ}s „ 16. -Q -5-Q -4-R isoxazole,

A> _Λ s , „16. -Q -3-Q -4-R isoxazole,

2-Q -5-Q^S-4-R pyrazole,

b s 19 4-Q -2-Q -5-R thiazole, and

^■t 1

2-Q -5-Q^S-4-R thiazole;

R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, triffuoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxy ethyl, and cyano; b 20 21 Q is selected from the group consisting of NR R , hydrido,

25 23 24 26 25 23 24

C(NR )NR R and N(R )C(NR )N(R )(R ), with the proviso that

20 21 no more than one of R and R is hydroxy, N-methylamino, and N,N-

23 24 dimethylamino at the same time and that no more than one of R and R is hydroxy, N-methylamino, and N,N-dimethylamino at the same time;

20 21 23 24 25 26 R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy, 2- aminoethyl, 2-(N-methylamino)ethyl, and 2-(N,N-dimethylamino)ethyl; g

Q is selected from the group consisting of a bond, CH₂, CH₂CH₂, CH₃CH, CF₃CH, CH₃CHCH₂, CF₃CHCH₂, CH₂(CH₃)CH, CH=CH, CF=CH, C(CH₃)=CH, CH=CHCH₂, CF=CHCH₂, C(CH₃)=CHCH₂, CH₂CH=CH, CH₂CF=CH, CH₂C(CH₃)=CH, CH₂CH=CHCH₂, CH₂CF=CHCH₂, CH₂C(CH₃)=CHCH₂, CH₂CH=CHCH₂CH₂, CH₂CF=CHCH₂CH₂, and CH₂C(CH₃)=CHCH₂CH₂.

In a more prefeπed specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to A is

32 optionally substituted by R , the other carbon adjacent to the carbon at the

point of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at

35 the point of attachment is optionally substituted by R , and any carbon

33 35 34 adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetiafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N~dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH3), N(OH),

CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃),

CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,23,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, and cyano;

„16 19 . . „ „_Λm25 _{T m}23„24 . , , . , _^16

R or R is optionally C(NR )NR R with the proviso that R ,

19 b R , and Q are not simultaneously hydrido;

_^ . _m 5 23 24 , _A . _, . , , . ,

Q is C(NR )NR R or hydπdo, with the proviso that no more than

23 24 one of R and R is hydroxy at the same time;

23 24 25

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, and hydroxy. In another more preferred specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selected from the group consisting of hydrido, ethyl, 2-propynyl,

2-ρropenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, l-methyl-2-butenyl, l-methyl-3-butenyl, l-methyl-2-butynyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-4-pentenyl, l-methyl-2-ρentynyl, l-methyl-3-pentynyl, 3-hexyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, l-propyl-2-propenyl, l-ethyl-2-butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, Sheptynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-5-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-4-pentenyl, l-butyl-2-proρenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl- 5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafιuorohexyl, and 3,3,3-trifluoropropyl, wherein each member of group B is optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to

32 33 34 35 36 A with one or more of the group consisting of R , R , R , R , and R ;

32 33 34 35 36

R ,R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-p^entafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxy ethyl, methoxycarbonyl, ethoxy carbonyl, amidocarbonyl, N-methylamidocarbonyl,

N,N-dimethylamidocarbonyl, cyano, and Q ;

A is selected from the group consisting of bond, NH, N(CH3), N(OH),

CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃),

CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

I f 17 1 10

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-pentafiuoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano;

R or R is optionally selected from the group consisting of NR R ,

C(NR )NR R , and N(R )C(NR )N(R )(R ), with the proviso that R ,

19 b

R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that no

_^20 . -,21 . , , , , , more than one of R and R is hydroxy at the same time and with the further

23 24 proviso that no more than one of R and R is hydroxy at the same time; 20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy.

In still another more prefeπed specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl, 2-moφholinyl, 3-moφholinyl, 4-moφholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyπolidinyl, 2-pyπolidinyl, 3 -pyπolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydroρyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbon is

33 optionally substituted with R , ring carbons and a nitrogen adjacent to the

9 carbon atom at the point of attachment are optionally substituted with R or

13 9

R , a ring carbon or nitrogen adjacent to the R position and two atoms from

the point of attachment is optionally substituted with R , and a ring carbon or

13 nitrogen adjacent to the R position and two atoms from the point of

12 attachment is optionally substituted with R ; 33 R is selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH3),

N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,

C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

16 17 18 1Q R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-peπtafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano;

., 16 19 . . „ _{^ ττ},25_x 23 24 . , , . , 16

R or R is optionally C(NR )NR R with the proviso that R ,

19 b R , and Q are not simultaneously hydrido; 95 2 94

Q is C(NR )NR R or hydrido, with the proviso that no more than

23 24 one of R and R is hydroxy at the same time;

23 24 25

R , R , andR are independently selected from the group consisting of hydrido, methyl, ethyl, and hydroxy. The more prefeπed specific embodiment compounds of Formula I having the formula:

or a pharmaceutically acceptable salt thereof, have common structural units, wherein;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, 0,

S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂; Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-ρyrimidinyl, 4-ρyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is

9 optionally substituted by R , the other carbon adjacent to the carbon at the point

13 9 of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by

10 13

R , a carbon adjacent to R and two atoms from the carbon at the point of ' 12 ' attachment is optionally substituted by R , and any carbon adjacent to both

Λ0 _{J T}.12 . . „ , . , , 1 1 R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,N-dimethyIamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,23,3,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetiafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxy ethyl, 2,2,2-trifluoro-l -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxy methyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l -hydroxyethyl, methoxycarbonyl, ethoxy carbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-ρhenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl,

N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy , cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulf onyl , 4-chlorophenylamino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy,

3,5-difluorophenoxy, 3, difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, ,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy, 3, dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-Smethylphenoxy , 4-fluorobenzyloxy,

2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy,

4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulf onyl, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3 ,5-bis-trifluoromethylbenzyloxy , 4-trifluoromethylphenoxy , 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 23,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy;

Y is selected from the group of formulas consisting of:

^■t Λ £l 1 ^7 i n 1 0

1-Q -4-Q^S-2-R -3-R -5-R -6-R benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

> , _Λs _{Λ ^}16 18 _Λ 19 . _Λ. 3-Q -6-Q -2-R -5-R -4-R pyπdme,

b s 16 18 Q -5-Q -3-R -6-R pyrazme,

_{^ ^} ^s _π18_^18 _Λ 19 ., . Q -6-Q -2-R -5-R -4-R pyndazme,

b s 17 18 Q -5-Q -4-R -6-R pyrimidine,

° -. ^s . _^16 _^ „19 . -2-Q -4-R -6-R pyπmidme,

b s 16 19 -5-Q -4-R -2-R thiophene,

b 16 17 -5_Q s -3 -R -4-R thiophene,

b s 16 19 -5-Q -4-R -2-R furan, ι 1 ι(- 1 ^7

2-Q -5-Q^S-3-R -4-R furan,

„ _Λb „ _Λs „ 16 _Λ 19

3-Q -5-Q -4-R -2-R pyπole,

₂_Q^b_5_Q^S-₃. « R16 -4 „-R¹⁷ pyπole,

4-Q -2-Q^S-5-R imidazole,

2-Q -4-Q^S-5-R imidazole,

„ b _ _^s _{Λ ^}16.

3-Q -5-Q -4-R isoxazole,

-Q -3-Q -4-R isoxazole,

2-Q^b-5-Q^S- 4 Λ- TR,¹⁶ pyrazole,

b s 19 4-Q -2-Q -5-R thiazole, and

2-Q -5-Q -4-R thiazole;

Q is selected from the group consisting of a bond, CH₂ and CH₂CH .

In a most prefeπed specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substituted by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substituted by R , a carbon

32 adj acent to R and two atoms from the carbon at the point of attachment is

35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ; τ,32 „33 34 35 _J 36 . _{J J} , , _{Λ p}

R , R , R , R , andR are independently selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo. amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH3), CH ,

CH₃CH, and CH₂CH₂; b 20 21 25 23 24

Q is NR R or C(NR )NR R ;

R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl.

In another most preferred specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3-hexyl, l-eιhyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,33-trifluoropropyl, wherein each member of group B is optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more

32 33 34 35 36 of the group consisting of R , R , R , R , and R ;

„32 33 34 35 36 . , _J ,

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH3), CH₂,

CH₃CH, and CH₂CH₂;

A is optionally selected from the group consisting of CH₂N(CH3),

CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that B is hydrido; b 20 21

Q is selected from the group consisting of NR R ,

25 23 24 26 25 23 24

C(NR )NR R , and N(R )C(NR )N(R )(R );

20 21 23 24 25 26 R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl.

In still another most prefeπed specific embodiment of Formula I, compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl, 2-moφholinyl, 3-moφholinyl, 4-moφholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piρeridinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyπolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3 -tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahy drothienyl, and 3-tetrahydrothienyl, wherein each

33 ring carbon is optionally substituted with R , ring carbons and a nitrogen adjacent to the carbon atom at the point of attachment are optionally substituted

9 13 9 with R or R , a ring carbon or nitrogen adjacent to the R position and two

atoms from the point of attachment are optionally substituted with R , and a

13 ring carbon or nitrogen atom adjacent to the R position and two atoms from

the potat of attactaent is optional substituted with R¹²;

33 R is selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano, and Q ; A is selected from the group consisting of a bond, NH, N(CH3), CH ,

CH₃CH, CH₂CH₂, and CH₂CH₂CH₂;

_^ . _ττ,20 21 _{^/ ττ},25_x 23_^24 Q is NR R or C(NR )NR R ;

20 21 23 24 25

The most prefeπed specific embodiment compounds of Formula I said compounds having the formula:

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro; R^ώ is selected from the group consisting of phenyl, 2-thienyl, 2-furyl,

2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to the 1,4-quinone ring is optionally substituted by

9

R , the other carbon adjacent to the carbon at the point of attachment is

13 9 optionally substituted by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is optionally substituted by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment is 12 10 12 . optionally substituted by R , and any carbon adjacent to both R and R is

11 optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy ethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino, dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and cyano;

Y is selected from the group of formulas consisting of:

> _{Λ ^}s _n 16 _n 17 „ 18 „ 19, -Q -4-Q -2-R -3-R -5-R -6-R benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

b _{^ ^}s „ 16 „ 18 „ „19 . ,. 3-Q -6-Q -2-R -5-R -4-R pyπdine,

-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene,

-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷thiophene,

-Q^b-5-Q^S-4-R¹⁶-2- R furan,

b s 16 _Λ \l_c -Q -5-Q -3 -R -4-R furan, 3-Q -5-Q -4-R -2-R pyπole,

_^16 _Λ „17

2-Q^b-5-Q^S- -R -4-R pyπole,

b s 19 4-Q -2-Q -5-R thiazole, and

2-Q^b-5-Q^S-4-R¹⁷thiazole;

16 _^17 18 , 19 R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano;

161 Q is CH₂.

The compounds of this invention can be used in anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular disease. The compounds of this invention can be used to inhibit serine protease associated with the coagulation cascade and factors II, VII, VIII, IX, X, XI, or XII. The compounds of the invention can inhibit the formation of blood platelet aggregates, inhibit the formation of fibrin, inhibit thrombus formation, and inhibiting embolus formation in a mammal, in blood, in blood products, and in mammalian organs. The compounds also can be used for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels in a mammal. The compounds can also be used in prophylactic treatment of subjects who are at risk of developing such disorders. The compounds can be used to lower the risk of atherosclerosis. The compounds of Formula (I) would also be useful in prevention of cerebral vascular accident (CVA) or stroke. Besides being useful for human treatment, these compounds are also useful for veterinary treatment of companion animals, exotic animals and farm animals, including mammals, rodents, and the like. More preferred animals include horses, dogs, and cats.

In yet another embodiment of the present invention, the novel compounds are selected from the compounds set forth in Table 1.

The use of generic terms in the description of the compounds are herein defined for clarity.

Standard single letter elemental symbols are used to represent specific types of atoms unless otherwise defined. The symbol "C" represents a carbon atom. The symbol "O" represents an oxygen atom. The symbol "N" represents a nitrogen atom. The symbol "P" represents a phosphorus atom. The symbol "S" represents a sulfur atom. The symbol "H" represents a hydrogen atom. Double letter elemental symbols are used as defined for the elements of the periodical table (i.e., Cl represents chlorine, Se represents selenium, etc.). As utilized herein, the term "alkyl", either alone or within other terms such as "haloalkyl" and "alkylthio", means an acyclic alkyl radical containing from 1 to about 10, preferably from 3 to about 8 carbon atoms and more preferably 3 to about 6 carbon atoms. Said alkyl radicals may be optionally substituted with groups as defined below. Examples of such radicals include methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec- butyl, tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl, octyl and the like.

The term "alkenyl" refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains at least one double bond. Such alkenyl radicals contain from about 2 to about 10 carbon atoms, preferably from about 3 to about 8 carbon atoms and more preferably 3 to about 6 carbon atoms. Said alkenyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkenyl radicals include propenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl, 2-2- methylbuten-1-yl, 3-methylbuten-l-yl, hexen-1-yl, 3-hydroxyhexen-l-yl, hepten-1- yl, and octen-1-yl, and the like.

The term "alkynyl" refers to an unsaturated, acyclic hydrocarbon radical in so much as it contains one or more triple bonds, such radicals containing about 2 to about 10 carbon atoms, preferably having from about 3 to about 8 carbon atoms and more preferably having 3 to about 6 carbon atoms. Said alkynyl radicals may be optionally substituted with groups as defined below. Examples of suitable alkynyl radicals include ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, pentyn-2-yl, 4- methoxypentyn-2-yl, 3-methylbutyn~l-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-l-yl radicals and the like.

The term "hydrido" denotes a single hydrogen atom (H). This hydrido radical may be attached, for example, to an oxygen atom to form a "hydroxyl" radical, one hydrido radical may be attached to a carbon atom to form a "methine" radical -CH=, or two hydrido radicals may be attached to a carbon atom to form a "methylene" (-CH₂-) radical.

The term "carbon" radical denotes a carbon atom without any covalent bonds and capable of forming four covalent bonds. The term "cyano" radical denotes a carbon radical having three of four covalent bonds shared by a nitrogen atom.

The term "hydroxyalkyl" embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with a hydroxyl as defined above. Specifically embraced are monohydroxyalkyl, dihydroxyalkyl and polyhydroxyalkyl radicals. The term "alkanoyl" embraces radicals wherein one or more of the terminal alkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylalkyl and dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicals include formyl, acetyl, and pentanoyl. Examples of dicarbonylalkyl radicals include oxalyl, malonyl, and succinyl.

The term "alkylene" radical denotes linear or branched radicals having from 1 to about 10 carbon atoms and having attachment points for two or more covalent bonds. Examples of such radicals are methylene, ethylene, methylethylene, and isopropylidene.

The term "alkenylene" radical denotes linear or branched radicals having from 2 to about 10 carbon atoms, at least one double bond, and having attachment points for two or more covalent bonds. Examples of such radicals are 1,1-vinylidene (CH₂=C), 1,2- vinylidene (-CH=CH-), and 1,4-butadienyl (-CH=CH-CH=CH-).

The term "halo" means halogens such as fluorine, chlorine, bromine or iodine atoms.

The term "haloalkyl" embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More preferred haloalkyl radicals are " haloalkyl" radicals having one to about six carbon atoms. Examples of such haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

The term "hydroxyhaloalkyl" embraces radicals wherein any one or more of the haloalkyl carbon atoms is substituted with hydroxy as defined above. Examples of "hydroxyhaloalkyl" radicals include hexafluorohydroxypropyl. The term "haloalkylene radical" denotes alkylene radicals wherein any one or more of the alkylene carbon atoms is substituted with halo as defined above. Dihalo alkylene radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkylene radicals may have more than two of the same halo atoms or a combination of different halo radicals. More prefeπed haloalkylene radicals are " haloalkylene" radicals having one to about six carbon atoms. Examples of "haloalkylene" radicals include difluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkyl substituted monofluoromethylene, and aryl substituted trifluoromethylene.

The term "haloalkenyl" denotes linear or branched radicals having from 1 to about 10 carbon atoms and having one or more double bonds wherein any one or more of the alkenyl carbon atoms is substituted with halo as defined above. Dihaloalkenyl radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhaloalkenyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. The terms "alkoxy" and "alkoxyalkyl" embrace linear or branched oxy- containing radicals each having alkyl portions of one to about ten carbon atoms, such as methoxy radical. The term "alkoxyalkyl" also embraces alkyl radicals having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More prefeπed alkoxy radicals are " alkoxy" radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyls. The "alkoxy" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "haloalkoxy" and "haloalkoxyalkyl" radicals. Examples of such haloalkoxy radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, and fluoropropoxy. Examples of such haloalkoxyalkyl radicals include fluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl, and trifluoroethoxy methyl. The terms "alkenyloxy" and "alkenyloxyalkyl" embrace linear or branched oxy-containing radicals each having alkenyl portions of two to about ten carbon atoms, such as ethenyloxy or propenyloxy radical. The term "alkenyloxyalkyl" also embraces alkenyl radicals having one or more alkenyloxy radicals attached to the alkyl radical, that is, to form monoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferred alkenyloxy radicals are " alkenyloxy" radicals having two to six carbon atoms. Examples of such radicals include ethenyloxy, propenyloxy, butenyloxy, and isopropenyloxy alkyls. The "alkenyloxy" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "haloalkenyloxy" radicals. Examples of such radicals include trifluoroethenyloxy, fluoroethenyloxy, difluoroethenyhloxy, and fluoropropenyloxy.

The term "haloalkoxyalkyl" also embraces alkyl radicals having one or more haloalkoxy radicals attached to the alkyl radical, that is, to form monohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term "haloalkenyloxy" also embraces oxygen radicals having one or more haloalkenyloxy radicals attached to the oxygen radical, that is, to form monohaloalkenyloxy and dihaloalkenyloxy radicals. The term "haloalkenyloxy alkyl" also embraces alkyl radicals having one or more haloalkenyloxy radicals attached to the alkyl radical, that is, to form monohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

The term "alkylenedioxy" radicals denotes alkylene radicals having at least two oxygens bonded to a single alkylene group. Examples of "alkylenedioxy" radicals include methylenedioxy, ethylenedioxy, alkylsubstituted methylenedioxy, and aryl substituted methylenedioxy. The term "haloalkylenedioxy" radicals denotes haloalkylene radicals having at least two oxy groups bonded to a single haloalkyl group. Examples of "haloalkylenedioxy" radicals include difluoromethylenedioxy, tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstituted monofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy. The term "aryl", alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused. The term "fused" means that a second ring is present (ie, attached or formed) by having two adjacent atoms in common (ie, shared) with the first ring. The term "fused" is equivalent to the term "condensed". The term "aryl" embraces aromatic radicals such as phenyl, naphthyi, tetrahydronaphthyl, indane and biphenyl.

The term "perhaloaryl" embraces aromatic radicals such as phenyl, naphthyi, tetrahydronaphthyl, indane and biphenyl wherein the aryl radical is substituted with 3 or more halo radicals as defined below. The term "heterocyclyl" embraces saturated and partially saturated heteroatom-containing ring-shaped radicals having from 4 through 15 ring members, herein referred to as "C4-C15 heterocyclyl", selected from carbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is a heteroatom. Heterocyclyl radicals may contain one, two or three rings wherein such rings may be attached in a pendant manner or may be fused. Examples of saturated heterocyclic radicals include saturated 3 to 6-membered heteromonocylic group containing 1 to 4 nitrogen atoms[e.g. pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. moφholinyl, etc.]; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partially saturated heterocyclyl radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. Non-limiting examples of heterocyclic radicals include 2-pyπolinyl, 3-pyπolinyl, pyπolindinyl, 13- dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl, moφholinyl, 1,4-dithianyl, thiomoφholinyl, and the like. Said "heterocyclyl" group may be substituted as defined herein. Prefeπed heterocyclic radicals include five to twelve membered fused or unfused radicals.

The term "heteroaryl" embraces fully unsaturated heteroatom-containing ring-shaped aromatic radicals having from 4 through 15 ring members selected from carbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is a heteroatom. Heteroaryl radicals may contain one, two or three rings wherein such rings may be attached in a pendant manner or may be fused. Examples of "heteroaryl" radicals, include the unsaturated heteromonocyclyl group of 5 to 6 contiguous members containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyπolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl [e.g., 4H-l,2,4-triazolyl, lH-l,23-triazolyl, 2H- 1,2,3-triazolyl, etc.] tetrazolyl [e.g. lH-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo [l,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to 6- membered heteromonocyclic group containing a sulfur atom, for example, 2- thienyl, 3-thienyl, etc.; unsaturated 5- to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 13,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 5 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g., 1,2,4- thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and the like. Said "heteroaryl" group may be substituted as defined herein. Prefeπed heteroaryl radicals include five and six membered unfused radicals. Non-limiting examples of heteroaryl radicals include 2- thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4- imidazolyl, 3-pyrazolyl, 4-pyrazolyl, l,2,4-triazol-3-yl, l,2,4-tiiazol-5-yl, 1,2,4- oxadiazol-3-yl, l,2,4-oxadiazol-5-yl, l,3,4-oxadiazol-3-yl, 13,4-oxadiazol-5-yl, 3-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 13,5-triazin-2-yl, l,2,4-triazin-3-yl, l,2,4-triazm-5-yl, l,2,4-triazin-6-yl, l,2,3-triazin-4-yl, and l,2,3-triazin-5-yl, and the like.

The term "sulfonyl", whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals -SO₂-. "Alkylsulfonyl", embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. "Alkylsulfonylalkyl", embraces alkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. "Haloalkylsulfonyl", embraces haloalkyl radicals attached to a sulfonyl radical, where haloalkyl is defined as above. "Haloalkylsulfonylalkyl", embraces haloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

The term "amidosulfonyl" embraces amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkyl cycloalkylamino, dicycloalkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, nitrogen containing heterocyclyl, heterocyclylamino, N-alkyl-N-heterocyclylamino, heteroarylammo, and heteroaralkylamino radicals, attached to one of two unshared bonds in a sulfonyl radical. The term "sulfinyl", whether used alone or linked to other terms such as alkylsulfinyl, denotes respectively divalent radicals -S(O)-. "Alkylsulfinyl", embraces alkyl radicals attached to a sulfinyl radical, where alkyl is defined as above. "Alkylsulfinylalkyl", embraces alkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. "Haloalkylsulfinyl", embraces haloalkyl radicals attached to a sulfinyl radical, where haloalkyl is defined as above. "Haloalkyl sulfinyl alkyl", embraces haloalkylsulfmyl radicals attached to an alkyl radical, where alkyl is defined as above.

The term "aralkyl" embraces aryl-substituted alkyl radicals. Preferable aralkyl radicals are " aralkyl" radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl and phenylmethyl are interchangeable.

The term "heteroaralkyl" embraces heteroaryl-substituted alkyl radicals wherein the heteroaralkyl radical may be additionally substituted with three or more substituents as defined above for aralkyl radicals. The term "perhaloaralkyl" embraces aryl-substituted alkyl radicals wherein the aralkyl radical is substituted with three or more halo radicals as defined above.

The term "aralkylsulfinyl", embraces aralkyl radicals attached to a sulfinyl radical, where aralkyl is defined as above. "Aralkylsulfinylalkyl", embraces aralkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above.

The term "aralkylsulfonyl", embraces aralkyl radicals attached to a sulfonyl radical, where aralkyl is defined as above. "Aralkylsulfonylalkyl", embraces aralkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term "cycloalkyl" embraces radicals having three to 15 carbon atoms. More prefeπed cycloalkyl radicals are " cycloalkyl" radicals having three to seven carbon atoms. Examples include radicals such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The term cycloalkyl embraces radicals having seven to 15 carbon atoms and having two to four rings. Exmaples incude radicals such as norbornyl (i.e., bicyclo[2.2.1]heptyl) and adamantyl. The term "cycloalkylalkyl" embraces cycloalkyl-substituted alkyl radicals. Preferable cycloalkylalkyl radicals are " cycloalkylalkyl" radicals having cycloalkyl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such radicals include cyclohexylhexyl. The term "cycloalkenyl" embraces radicals having three to ten carbon atoms and one or more carbon-carbon double bonds. Prefeπed cycloalkenyl radicals are " cycloalkenyl" radicals having three to seven carbon atoms. Examples include radicals such as cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl. The term "halocycloalkyl" embraces radicals wherein any one or more of the cycloalkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. A monohalocycloalkyl radical, for one example, may have either a bromo, chloro or a fluoro atom within the radical. Dihalo radicals may have two or more of the same halo atoms or a combination of different halo radicals and polyhalocycloalkyl radicals may have more than two of the same halo atoms or a combination of different halo radicals. More prefeπed halocycloalkyl radicals are " halocycloalkyl" radicals having three to about eight carbon atoms. Examples of such halocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl, trifluorocyclopentyl, tetrafluorocyclohexyl, and dichlorocyclopropyl. The term "halocycloalkenyl" embraces radicals wherein any one or more of the cycloalkenyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl and polyhalocycloalkenyl radicals.

The term "cycloalkoxy" embraces cycloalkyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexoxy and cyclopentoxy. The term "cycloalkoxyalkyl" also embraces alkyl radicals having one or more cycloalkoxy radicals attached to the alkyl radical, that is, to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals. Examples of such radicals include cyclohexoxy ethyl. The "cycloalkoxy" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "halocycloalkoxy" and "halocycloalkoxyalkyl" radicals.

The term "cycloalkylalkoxy" embraces cycloalkyl radicals attached to an alkoxy radical. Examples of such radicals includes cyclohexylmethoxy and cyclopentylmethoxy.

The term "cycloalkenyloxy" embraces cycloalkenyl radicals attached to an oxy radical. Examples of such radicals includes cyclohexenyloxy and cyclopentenyloxy. The term "cycloalkenyloxyalkyl" also embraces alkyl radicals having one or more cycloalkenyloxy radicals attached to the alkyl radical, that is, to form monocycloalkenyloxyalkyl and dicycloalkenyloxyalkyl radicals. Examples of such radicals include cyclohexenyloxyethyl. The "cycloalkenyloxy" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "halocycloalkenyloxy" and "halocycloalkenyloxyalkyl" radicals.

The term "cycloalkylenedioxy" radicals denotes cycloalkylene radicals having at least two oxygens bonded to a single cycloalkylene group. Examples of "alkylenedioxy" radicals include 1,2-dioxycyclohexylene.

The term "cycloalkylsulfinyl", embraces cycloalkyl radicals attached to a sulfinyl radical, where cycloalkyl is defined as above. "Cycloalkylsulfinylalkyl", embraces cycloalkylsulfinyl radicals attached to an alkyl radical, where alkyl is defined as above. The term "Cycloalkylsulfonyl", embraces cycloalkyl radicals attached to a sulfonyl radical, where cycloalkyl is defined as above. "Cycloalkylsulfonylalkyl", embraces cycloalkylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

The term "cycloalkylalkanoyl" embraces radicals wherein one or more of the cycloalkyl carbon atoms are substituted with one or more carbonyl radicals as defined below. Specifically embraced are monocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples of monocarbonylcycloalkyl radicals include cyclohexylcarbonyl, cyclohexylacetyl, and cyclopentylcarbonyl. Examples of dicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

The term "alkylthio" embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent sulfur atom. More preferred alkylthio radicals are " alkylthio" radicals having one to six carbon atoms. An example of " alkylthio" is methylthio (CH₃-S-). The "alkylthio" radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide "haloalkylthio" radicals. Examples of such radicals include fluoromethylthio, chloromethylthio, trifluoromethylthio, difluoromethylthio, trifluoroethylthio, fluoroethylthio, tetrafluoroethylthio, pentafluoroethylthio, and fluoropropylthio.

The term "alkyl aryl amino" embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, and one aryl radical both attached to an amino radical. Examples include N-methyl-4-methoxyaniline, N- ethyl-4-methoxyaniline, and N-methyl-4-trifluoromethoxyaniline.

The term alkylamino denotes "monoalkylamino" and "dialkylamino" containing one or two alkyl radicals, respectively, attached to an amino radical.

One or two alkyl radicals of the alkylamino may be optionally substituted with hydrogen bonding substitutents selected from the group consisting of hydroxy, amino, monoalkylamino, dialkylamino, amidino, guanidino, thiol, and alkoxy provided the alkyl radicals comprises two or more carbons.

The terms ai lamino denotes "monoarylamino" and "diarylamino" containing one or two aryl radicals, respectively, attached to an amino radical. Examples of such radicals include N-phenylamino and N-naphthylamino.

The term "aralkyla ino", embraces aralkyl radicals attached to an amino radical, where aralkyl is defined as above. The term aralkylamino denotes "monoaralkylamino" and "diaralkylamino" containing one or two aralkyl radicals, respectively, attached to an amino radical. The term aralkylamino further denotes "monoaralkyl monoalkylamino" containing one aralkyl radical and one alkyl radical attached to an amino radical.

The term "arylsulfinyl" embraces radicals containing an aryl radical, as defined above, attached to a divalent S(O) atom. The term "arylsulfinylalkyl" denotes arylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms.

The term "arylsulfonyl", embraces aryl radicals attached to a sulfonyl radical, where aryl is defined as above, "arylsulfonylalkyl", embraces arylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above. The term "heteroarylsulfinyl" embraces radicals containing an heteroaryl radical, as defined above, attached to a divalent S(O) atom. The term "heteroarylsulfinylalkyl" denotes heteroarylsulfinyl radicals attached to a linear or branched alkyl radical, of one to ten carbon atoms. The term "Heteroarylsulfonyl", embraces heteroaryl radicals attached to a sulfonyl radical, where heteroaryl is defined as above. "Heteroarylsulfonylalkyl", embraces heteroarylsulfonyl radicals attached to an alkyl radical, where alkyl is defined as above.

The term "aryloxy" embraces aryl radicals, as defined above, attached to an oxygen atom. Examples of such radicals include phenoxy, 4-chloro-3- ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloro-4-ethylphenoxy, 3,4- dichlorophenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy, 3- trifluoromethylphenoxy, 4-fluoroρhenoxy, 3,4-dimethylphenoxy, 5-bromo-2- fiuorophenoxy, 4-bromo-3-fluorophenoxy, 4-fluoro-3-methylρhenoxy, 5,6,7,8- tetrahydronaphthyloxy, 3-isopropylphenoxy, 3-cyclopropylphenoxy, 3- ethylphenoxy, 3-pentafluoroethylphenoxy, 3-( 1 , 1 ,2,2-tetrafluoroethoxy)- phenoxy, and 4-tert -butylphenoxy. The term "aroyl" embraces aryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include benzoyl and toluoyl.

The term "aralkanoyl" embraces aralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, phenylacetyl.

The term "aralkoxy" embraces oxy-containing aralkyl radicals attached through an oxygen atom to other radicals. More prefeπed aralkoxy radicals are " aralkoxy" radicals having phenyl radicals attached to alkoxy radical as described above. Examples of such radicals include benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy, 3-trifluoromethylbenzyloxy, 3,5- difluorobenyloxy, 3-bromobenzyloxy, 4-propylbenzyloxy, 2-fluoro-3- trifluoromethylbenzyloxy, and 2-phenylethoxy.

The term "aryloxyalkyl" embraces aryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenoxymethyl.

The term "haloaryloxyalkyl" embraces aryloxyalkyl radicals, as defined above, wherein one to five halo radicals are attached to an aryloxy group.

The term "heteroaroyl" embraces heteroaryl radicals, as defined above, attached to an carbonyl radical as defined above. Examples of such radicals include furoyl and nicotinyl.

The term "heteroaralkanoyl" embraces heteroaralkyl radicals, as defined herein, attached to an carbonyl radical as defined above. Examples of such radicals include, for example, pyridylacetyl and furylbutyryl.

The term "heteroaralkoxy" embraces oxy-containing heteroaralkyl radicals attached through an oxygen atom to other radicals. More preferred heteroaralkoxy radicals are " heteroaralkoxy" radicals having heteroaryl radicals attached to alkoxy radical as described above. The term

"heterocyclylalkoxy" embraces oxy-containing heterocyclylalkyl radicals attached through an oxygen atom to other radicals. The term "haloheteroaryloxyalkyl" embraces heteroaryloxyalkyl radicals, as defined above, wherein one to four halo radicals are attached to an heteroaryloxy group.

The term " heteroarylamino" embraces heteroaryl radicals, as defined above, attached to an amino group. Examples of such radicals include pyridylamino. The term "heterocyclylamino" embraces heterocyclyl radicals, as defined above, attached to an amino group. The term "heteroaralkylamino" embraces heteroaralkyl radicals, as defined above, attached to an amino group. Examples of such radicals include pyridylmethylamino. The term "heterocyclylalkylamino" embraces heterocyclylalkyl radicals, as defined above, attached to an amino group. The term "heteroaryloxy" embraces heteroaryl radicals, as defined above, attached to an oxy group. Examples of such radicals include 2- thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and 4-pyridyloxy. The term "heterocyclyloxy" embraces heterocyclyl radicals, as defined above, attached to an oxy group. The term "heteroaryloxyalkyl" embraces heteroaryloxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include 2- pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl. The term "heterocyclyloxyalkyl" embraces heterocyclyloxy radicals, as defined above, attached to an alkyl group. The term "arylthio" embraces aryl radicals, as defined above, attached to an sulfur atom. Examples of such radicals include phenylthio.

The term "arylthioalkyl" embraces arylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include phenylthiomethyl. The term "alkylthioalkyl" embraces alkylthio radicals, as defined above, attached to an alkyl group. Examples of such radicals include methylthiomethyl. The term "alkoxyalkyl" embraces alkoxy radicals, as defined above, attached to an alkyl group. Examples of such radicals include methoxymethyl. The term "carbonyl" denotes a carbon radical having two of the four covalent bonds shared with an oxygen atom. The term "carboxy" embraces a hydroxyl radical, as defined above, attached to one of two unshared bonds in a carbonyl group. The term "carboxamido" embraces amino, monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino, dicycloalkylamino, N- alkyl-N-arylamino, arylamino, aralkylamino, nitrogen containing heterocyclyl, heterocyclylamino, N-alkyl-N-heterocyclylamino, heteroarylamino, and heteroaralkylamino radicals, attached to one of two unshared bonds in a carbonyl group. The term "carboxamidoalkyl" embraces carboxamido radicals, as defined above, attached to an alkyl group. The term "carboxyalkyl" embraces a carboxy radical, as defined above, attached to an alkyl group. The term "carboalkoxy" embraces alkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term "carboaralkoxy" embraces aralkoxy radicals, as defined above, attached to one of two unshared bonds in a carbonyl group. The term "monocarboalkoxyalkyl" embraces one carboalkoxy radical, as defined above, attached to an alkyl group. The term "dicarboalkoxyalkyl" embraces two carboalkoxy radicals, as defined above, attached to an alkylene group. The term "monocyanoalkyl" embraces one cyano radical, as defined above, attached to an alkyl group. The term "dicyanoalkylene" embraces two cyano radicals, as defined above, attached to an alkyl group. The term "carboalkoxycyanoalkyl" embraces one cyano radical, as defined above, attached to an carboalkoxyaikyl group. The term "acyl", alone or in combination, means a carbonyl or thionocarbonyl group bonded to a radical selected from, for example, hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy, arylthio, and alkylthioalkyl. Examples of "acyl" are formyl, acetyl, benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like. The term "haloalkanoyl" embraces one or more halo radicals, as defined herein, attached to an alkanoyl radical as defined above. Examples of such radicals include, for example, chloroacetyl, trifluoroacetyl, bromopropanoyl, and heptafluorobutanoyl. The term "phosphono" embraces a pentavalent phosphorus attached with two covalent bonds to an oxygen radical. The term "dialkoxyphosphono" denotes two alkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term "diaralkoxyphosphono" denotes two aralkoxy radicals, as defined above, attached to a phosphono radical with two covalent bonds. The term "dialkoxyphosphonoalkyl" denotes dialkoxyphosphono radicals, as defined above, attached to an alkyl radical. The term "diaralkoxyphosphonoalkyl" denotes diaralkoxyphosphono radicals, as defined above, attached to an alkyl radical.

The term "amino" denotes a nitrogen atom containing two substituents such as hydrido, hydroxy or alkyl and having one covalent bond available for bonding to a single atom such as carbon. Examples of such amino radicals include, for example, -NH₂, -NHCH₃, -NHOH, and -NHOCH3. The term "imino" denotes a nitrogen atom containing one substituent such as hydrido, hydroxy or alkyl and having two covalent bonds available for bonding to a single atom such as carbon. Examples of such imino radicals include, for example, =NH, =NCH₃ , =NOH, and =NOCH₃. The term "imino carbonyl" denotes a carbon radical having two of the four covalent bond sites shared with an imino group. Examples of such imino carbonyl radicals include, for example, C=NH, C=NCH₃ , C=NOH, and C=NOCH₃. The term "amidino" embraces a substituted or unsubstituted amino group bonded to one of two available bonds of an iminocarbonyl radical. Examples of such amidino radicals include, for example, NH₂-C=NH, NH₂-

C=NCH₃, NH₂-C=NOCH₃ and CH₃NH-C=NOH. The term "guanidino" denotes an amidino group bonded to an amino group as defined above where said amino group can be bonded to a third group. Examples of such guanidino radicals include, for example, NH₂-C(NH)-NH-, NH₂-C(NCH₃)-NH-, NH₂-C(NOCH₃)- NH-, and CH₃NH-C(NOH)-NH-.

The term "suffonium" denotes a positively charged trivalent sulfur atom where said sulfur is substituted with three carbon based groups such as alkyl, alkenyl, aralkyl, or aryl. The term "dialkyl suffonium" denotes a suffonium group where said sulfur is substituted with two alkyl groups. Examples of such dialkylsulfonium radicals include, for example, (CH₃)₂S -. The term "dialkyl sulfonium alkyl" denotes a dialkyl sulfonium group where said group is bonded to one bond of an alkylene group as defined above. Examples of such

. dialkylsulfoniumalkyl radicals include (CH₃)₂S -CH₂CH₂-.

The term "phosphonium" denotes a positively charged tetravalent phosphorus atom where said phosphorus is substituted with four carbon based groups such as alkyl, alkenyl, aralkyl, or aryl. The term "trialkyl phosphonium" denotes a phosphonium group where said phosphorus is substituted with three alkyl groups. Examples of such trialkylphosphonium radicals include, for example,

(CH₃)₃P⁺-. Said "alkyl", "alkenyl", "alkynyl", "alkanoyl", "alkylene",

"alkenylene", "hydroxyalkyl", "haloalkyl", "haloalkylene", "haloalkenyl", "alkoxy", "alkenyloxy", "alkenyloxyalkyl", "alkoxyalkyl", "aryl", "perhaloaryl", "haloalkoxy", "haloalkoxyalkyl", "haloalkenyloxy", "haloalkenyloxyalkyl", "alkylenedioxy", "haloalkylenedioxy", "heterocyclyl", "heteroaryl", "hydroxyhaloalkyl", "alkylsulfonyl", "haloalkylsulfonyl", "alkylsulfonylalkyl", "haloalkylsulfonylalkyl", "alkylsulfinyl", "alkylsulfinylalkyl", "haloalkylsulfinylalkyl", "aralkyl", "heteroaralkyl", "perhaloaralkyl", "aralkylsulfonyl", "aralkylsulfonylalkyl", "aralkylsulfinyl", "aralkylsulfinylalkyl", "cycloalkyl", "cycloalkylalkanoyl", "cycloalkylalkyl", "cycloalkenyl", "halocycloalkyl", "halocycloalkenyl", "cycloalkylsulfinyl", "cycloalkylsulfinylalkyl", "cycloalkylsulfonyl", "cycloalkylsulfonylalkyl", "cycloalkoxy", "cycloalkoxyalkyl", "cycloalkylalkoxy", "cycloalkenyloxy", "cycloalkenyloxyalkyl", "cycloalkylenedioxy", "halocycloalkoxy", "halocycloalkoxyalkyl", "halocycloalkenyloxy", "halocycloalkenyloxyalkyl", "alkylthio", "haloalkylthio", "alkylsulfinyl", "amino", "oxy", "thio", "alkylamino", "arylamino", "aralkylamino", "arylsulfinyl", "arylsulfinylalkyl", "arylsulfonyl", "arylsulfonylalkyl", "heteroarylsulfinyl",

"heteroarylsulfinylalkyl", "heteroarylsulfonyl", "heteroarylsulfonylalkyl ", "heteroarylamino", "heteroaralkylamino", "heteroaryloxy", "heteroaryloxylalkyl", "aryloxy", "aroyl", "aralkanoyl", "aralkoxy", "aryloxyalkyl", "haloaryloxy alkyl", "heteroaroyl", "heteroaralkanoyl", "heteroaralkoxy", "heteroaralkoxyalkyl", "arylthio", "arylthioalkyl", "alkoxyalkyl", "acyl", "amidino", "guanidino", "dialkylsulfonium", "trialkylphosphonium", and "dialkylsulfoniumalkyl" groups defined above may optionally have 1 or more non-hydrido substituents such as amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N- alkylamino, heteroaralkylamino, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroaralkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl. The term "spacer" can include a covalent bond and a linear moiety having a backbone of 1 to 7 contiguous atoms. The spacer may have 1 to 7 atoms of a univalent or multi-valent chain. Univalent chains may be constituted by a radical selected from =C(H)-, =C(R^2&)-, -O-, -S-, -S(O)-, -S(O)₂-,

2a 2a 2a

-NH-, -N(R )-, -N=, -CH(OH)-, =C(OH)-, -CH(OR )-, =C(OR )-, and

2a -C(O)- wherein R is selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl, alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl, heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, and heteroarylalkenyl. Multi-valent chains may consist of a straight chain of 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2 or 3 or 4 or 5 or 6 atoms with a side chain. The chain may be constituted of one or more radicals selected from: alkylene, alkenyl, -O-, -O-CH₂-, -S-CH₂-, -CH₂CH₂-, ethenyl,

-CH=CH(OH)-, -OCH₂O-, -O(CH₂)₂O-, -NHCH₂-, -OCH(R^2a)O-,

2a -O(CH₂CHR )O-, -OCF₂O-, -O(CF₂)₂O-, -S-, -S(O)-, -S(O)₂-, -N(H ,

2a 2a 2a -N(H)O-, -N(R )O-, -N(R )-, -C(O)-, -C(O)NH-, -C(O)NR -, -N=,

-OCH₂-, -SCH₂-, S(O)CH₂-, -CH₂C(O)-, -CH(OH)-, =C(OH)-, -CH(OR^2a)-,

2a 2a

=C(OR )-, S(O)₂CH₂-, and -NR CH₂- and many other radicals defined above or generally known or ascertained by one of skill-in-the art. Side chains may include substituents such as 1 or more non-hydrido substituents such as amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroaralkylamino, heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio, nitro, alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfmylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxy aralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

Compounds of the present invention can exist in teutomeric, geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and trans-geometric isomers, E- and Z-geometric isomers, R- and S- enantiomers, diastereomers, d-isomers, 1-isomers, the racemic mixtures thereof and other mixtures thereof, as falling within the scope of the invention. Pharmaceutically acceptable sales of such tautomeric, geometric or stereoisomeric forms are also included within the invention.

The terms "cis" and "trans" denote a form of geometric isomerism in which two carbon atoms connected by a double bond will each have a hydrogen atom on the same side of the double bond ("cis") or on opposite sides of the double bond ("trans").

Some of the compounds described contain alkenyl groups, and are meant to include both cis and trans or "E" and "Z" geometric forms. Some of the compounds described contain one or more stereocenters and are meant to include R, S, and mixtures of R and S forms for each stereocenter present.

Some of the compounds described herein may contain one or more ketonic or aldehydic carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the "keto" form and in part or principally as one or more

"enol" forms of each aldehyde and ketone group present. Compounds of the present invention having aldehydic or ketonic carbonyl groups are meant to include both "keto" and "enol" tautomeric forms. Some of the compounds described herein may contain one or more amide carbonyl groups or combinations thereof alone or as part of a heterocyclic ring system. Such carbonyl groups may exist in part or principally in the "keto" form and in part or principally as one or more "enol" forms of each amide group present. Compounds of the present invention having amidic carbonyl groups are meant to include both "keto" and "enol" tautomeric forms. Said amide carbonyl groups may be both oxo (C=O) and thiono (C=S) in type.

Some of the compounds described herein may contain one or more imine or enamine groups or combinations thereof. Such groups may exist in part or principally in the "imine" form and in part or principally as one or more "enamine" forms of each group present. Compounds of the present invention having said imine or enamine groups are meant to include both

"imine" and "enamine" tautomeric forms.

Compounds of the present invention described herein are 1,4-quinones. 1 ,4-Quinone compounds, which can be considered to be diketones of an arene compound and are well-known (for example, in the simplest specific case where the parent aromatic compound is benzene, the 1,4-quinone isl,4-benzoquinone).

1,4-Quinones are known to commonly undergo facile reduction to 1,4- hydroquinones via both chemical and biochemical processes. A 1,4- hydroquinone is in reality a 1,4-dihydroxyarene; in a specific case, the 1,4- hydroquinone of benzene is called 1,4-dihydoxybenzene or 1,4-benzoquinone. 1,4-Hydroquinones are also known to undergo facile chemical or biochemical oxidation to the 1,4-quinones. Interconversions of quinones to hydroquinones and vice versa through oxidations and reductions are also well-known in the chemical literature and in biological processes. 1,4-Quinone compounds of the present invention having two carbonyls groups are considered to encompass the corresponding 1,4-hydroquinone compounds or forms.

The present invention also comprises a treatment and prophylaxis in anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular disease in a subject, comprising administering to the subject having such disorder a therapeutically- effective amount of a compound of Formula (I):

or a pharmaceutically-acceptable salt thereof.

As a further embodiment, compounds of the present invention of Formula (I) or a pharmaceutically-acceptable salt thereof as defined above, comprise a treatment and prophylaxis of coronary artery disease, cerebrovascular disease and other coagulation cascade related disorders in a subject, comprising administering to the subject having such disorder a therapeutically-effective amount of compounds of formula (I) of the present invention or a pharmaceutically-acceptable salt thereof.

Compounds of the present invention of Formula (I) or a pharmaceutically-acceptable salt thereof can also be used whenever inhibition of blood coagulation is required such as to prevent coagulation of stored whole blood and to prevent coagulation in other biological samples for testing or storage. Thus coagulation inhibitors of the present inhibition can be added to or contacted with stored whole blood and any medium containing or suspected of containing plasma coagulation factors and in which it is desired that blood coagulation be inhibited, e.g. when contacting the mammal's blood with material selected from the group consisting of vascular grafts, stents, orthopedic prothesis, cardiac prosthesis, and extracoφoreal circulation systems.

Compounds of Formula (I) are capable of inhibiting activity of serine proteases related to the coagulation cascade, and thus could be used in the manufacture of a medicament, a method for the prophylactic or therapeutic treatment of diseases mediated by coagulation cascade serine proteases, such as inhibiting the formation of blood platelet aggregates, inhibiting the formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, in blood, in blood products, and in mammalian organs. The compounds also can be used for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels in a mammal. The compounds also can be used to study the mechanism of action of coagulation cascade serine proteases to enable the design of better inhibitors and development of better assay methods. The compounds of Formula (I) would be also useful in prevention of cerebral vascular accident (CVA) or stroke.

Also included in the family of compounds of Formula (I) are the pharmaceutically-acceptable salts thereof. The term "phaπnaceutically- acceptable salt" embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula (I) may be prepared from inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, examples of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic, cyclohexylaminosulfonic, algenic, galacturonic acid. Suitable pharmaceutically- acceptable base addition salts of compounds of Formula (I) include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N'-dibenzylethyleneldiamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N- methylglucamine) and procain. All of these salts may be prepared by conventional means from the coπesponding compound of Formula (I) by reacting, for example, the appropriate acid or base with the compound of Formula (I).

The present invention also comprises a pharmaceutical composition comprising a therapeutically-effective amount of a compound of Formulas (I) in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent. Pharmaceutical compositions of the present invention can comprise the active compounds of Formula (I) in association with one or more non-toxic, pharmaceutically-acceptable carriers and/or diluents and/or adjuvants (collectively refeπed to herein as "carrier" materials) and, if desired, other active ingredients. The active compounds of the present invention may be administered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, and in a dose effective for the treatment intended.

The active compounds and composition may, for example, be administered orally, intravascularly, intraperitoneaily, subcutaneously, intramuscularly, oculary, or topically. For treating ocular build up of fibrin, the compounds may be administered intraocularly or topically as well as orally or parenterally.

The compounds can be administered in the form of a depot injection or implant preparation which may be formulated in such a manner as to permit a sustained release of the active ingredient. The active ingredient can be compressed into pellets or small cylinders and implanted subcutaneously or intramusculary as depot injections or implants. Implants may employ inert materials such as biodegradable polymers or synthetic silicones, for example, Silastic, silicone rubber or other silicon containing polymers. The compounds can also be administered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines. The compounds may also be delivered by the use of monoclonal antibodies as individual carriers to which the compound molecules are coupled. The compounds may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyπolidone, pyran copolymer, polyhydroxy-propyl-methacrylamide-phenol, polyhydroxyethyl-aspartamide- phenol, or ployethyleneoxide-polylysine substituted with palmitoyl residues. Furthermore, the compounds may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross linked or amphitpathic block copolymers of hydrogels. For oral administration, the pharmaceutical composition may be in the form of, for example, tablets, capsules (each of which includes sustained release or timed release formulations), pills, powders, granules, elixers, tinctures, suspensions, liquids including syrups, and emulsions. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient. Examples of such dosage units are tablets or capsules. The active ingredient may also be administered by injection as a composition wherein, for example, saline, dextrose or water may be used as a suitable carrier.

The amount of therapeutically active compounds which are administered and the dosage regimen for treating a disease condition with the compounds and/or compositions of this invention depends on a variety of factors, including the age, weight, sex and medical condition of the subject, the severity of the disease, the route and frequency of administration, and the particular compound employed, and thus may vary widely. The pharmaceutical compositions may contain active ingredients in the range of about 0.1 to 2000 mg, and preferably in the range of about 0.5 to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, and preferably between about 0.5 and about 20 mg/kg body weight, may be appropriate. The daily dose can be administered in one to four doses per day. The compounds may be formulated in topical ointment or cream, or as a suppository, containing the active ingredients in a total amount of, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably 0.4 to 15% w/w. When formulated in an ointment, the active ingredients may be employed with either paraffmic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example at least 30% w/w of a polyhydric alcohol such as propylene glycol, butane- 13-diol, mannitol, sorbitol, glycerol, polyethylene glycol and mixtures thereof. The topical formulation may desirably include a compound which enhances absoφtion or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsulf oxide and related analogs. The compounds of this invention can also be administered by a transdermal device. Preferably topical administration will be accomplished using a patch either of the reservoir and porous membrane type or of a solid matrix variety. In either case, the active agent is delivered continuously from the reservoir or microcapsules through a membrane into the active agent permeable adhesive, which is in contact with the skin or mucosa of the recipient. If the active agent is absorbed through the skin, a controlled and predetermined flow of the active agent is administered to the recipient. In the case of microcapsules, the encapsulating agent may also function as the membrane.

The oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner. While the phase may comprise merely an emulsifier, it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer. It is also prefeπed to include both an oil and a fat. Together, the emulsifier(s) with or without stabilizer(s) make-up the so-called emulsifying wax, and the wax together with the oil and fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations. Emulsifiers and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate, among others.

The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Thus, the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as diisoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethyIhexyl palmitate or a blend of branched chain esters may be used. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and/or liquid paraffin or other mineral oils can be used.

For therapeutic p poses, the active compounds of the present invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered per os, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, poly vinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient administration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of administration are well and widely known in the pharmaceutical art

In practicing the methods of the present invention for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular disease, the compounds and pharmaceutical compositions of the present invention are administered alone or in combination with one another, or in combination with other therapeutics or in vivo diagnostic agents. The coagulation cascade inhibitors of the present invention can also be co- administered with suitable anti-platelet agreggation agents, including, but not limited to ticlopidine or clopidrogel, fibrinogen receptor antagonists (e.g. to treat or prevent unstable angina or to prevent reocculsion after angioplasty and restenosis), anti-coagulants such as aspirin, warfarin or heparins, thrombolytic agents such as plasminogen activators or streptokinase to achieve synergistic effects in the treatment of various pathologies, lipid lowering agents including antihypercholesterolemics (e.g. HMG CoA reductase inhibitors such as mevastatin, lovastatin, simvastatin, pravastatin, andfluvastatin, HMG CoA synthatase inhibitors, etc.), anti-diabetic drugs, or other cardiovascular agents (loop diuretics, thiazide type diuretics, nitrates, aldosterone antagonistics (i.e., spironolactone and epoxymexlerenone), angiotensin converting enzyme (e.g. ACE) inhibitors, angiotensin II receptor antagonists, beta-blockers, antiarrythmics, anti-hypertension agents, and calcium channel blqckers) to treat or prevent atheriosclerosis. For example, patients suffering from coronary artery disease, and patients subjected to angioplasty procedures, would benefit from coadministration of fibrinogen receptor antagonists and coagulation cascade inhibitors of the present invention. Also, coagulation cascade inhibitors could enhance the efficiency of tissue plasminogen activator-mediated thrombolytic reperfusion.

Typical doses of coagulation cascade inhibitors of the present invention with other suitable anti-platelet agents, anticoagulation agents, cardiovascular therapeutic agents, or thrombolytic agents may be the same as those doses of coagulation cascade inhibitors administered without coadministration of additional anti-platelet agents, anticoagulation agents, cardiovascular therapeutic agents, or thrombolytic agents, or may be substantially less than those doses of coagulation cascade inhibitors administered without coadministration of additional anti-platelet agents, anticoagulation agents, cardiovascular therapeutic agents, or thrombolytic agents, depending on a patient's therapeutic needs. The present novel methods preferably employ compounds which selectively inhibit human TF-VIIA over the inhibition of both human Thrombin II and human factor Xa. Preferably, the compounds have a human TF-VIIA

IC₅₀ of less than 0.5 μM and also have a selectivity ratio of TF-VIIA inhibition over both human Thrombin II and human factor Xa inhibition of at least 10, and more preferably at least 100. Even more preferably, the compounds have a human TF-VIIA IC₅₀ of less than 0.1 μM and also have a selectivity ratio of

TF-VIIA inhibition over both human Thrombin II and human factor Xa inhibition of at least 1000, and most preferably at least 10,000. All mentioned references are incoφorated by reference as if here written.

Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations. The following examples are provided to illustrate the present invention and are not intended to limit the scope thereof. Without further elaboration, it is believed that one skilled in the art can, using the preceding descriptions, utilize the present invention to its fullest extent. Therefore the following prefeπed specific embodiments are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. Compounds containing multiple variations of the structural modifications illustrated in the schemes or the following Examples are also contemplated. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. One skilled in the art may use these generic methods to prepare the following specific examples, which have been or may be properly characterized by *H NMR, mass spectrometry, elemental composition, and similar procedures. These compounds also may be formed in vivo. The following examples contain detailed descriptions of the methods of preparation of compounds of Formula (I). These detailed descriptions fall within the scope and are presented for illustrative puφoses only and are not intended as a restriction on the scope of the invention. All parts are by weight and temperatures are Degrees centigrade unless otherwise indicated.

The following general synthetic sequences are useful in making the present invention. Abbreviations used in the schemes and tables include: "AA" represents amino acids, "AcCN" represents acetonitrile, "AcOH" represents acetic acid, "BINAP" represents 2,2'-bis(diphenylphosphino)-l,l'-binaphthyl, "BnOH" represents' benzyl alcohol, "BnCHO" represents 2-phenylethanal, "

BnSO₂Cl" represents benzylsulfonyl chloride, "Boc" represents tert- butyloxy carbonyl, "BOP" represents benzotriazol-1-yl-oxy-tris-

(dimethylamino), "bu" represents butyl, "dba" represents dibenzylidene- acetone, "DCC" represents 1,3-dicyclohexylcarbodiimide, "DCM" represents dichloromethane or methylene chloride, "DIBAH" or "DIBAL" represents diisobutylaluminum hydride, "DMF" represents dimethylf ormamide, "DMSO" represents dimethylsulf oxide, "DPPA" represents diphenylphosphoryl azide", "EDC" represents l-[3-(dimethylamino)propyl]- 3-ethylcarbodiimide hydrochloride, "Ex. No." represents Example Number, "Fmoc" represents 9-fIuorenylmethoxycarbonyl, "HOBt" represents hydroxybenzoltriazole", "LDA" represents lithium diisopropylamide, "MCPBA" represents meta-chloroperbenzoic acid, "MW" represents molecular weight, "NMM" represents N-methylmoφholine, "Ph" represents phenyl or aryl, "PHTH" represents a phthaloyl group, "pnZ" represents 4- nitrobenzyloxy-carbonyl, "PTC" represents a phase transfer catalyst , "py" represents pyridine, " RNH₂" represents a primary organic amine, "p-

TsOH" represents paratoluenesulfonic acid, ' BAF" represents tetrabutylammonium fluoride, "TBTU" represents 2-(lH-benzotriozole-l-yl)- 1,1,33-tetramethyl uronium tetrafluoroborate, "TEA" represents triethylamine, ' FA" represents trifluoroacetic acid, "THF" represents tetrahydrofuran, ' MS" represents trimethylsilyl, "TMSCN" represents trimethylsilyl cyanide, and "Cbz" or "Z" represents benzyloxycarbonyl.

GENERAL SYNTHETIC PROCEDURES AND SPECIFIC EXAMPLES

The 1 ,4-quinone compounds of the present invention can be synthesized, for example, according to the following procedures and Schemes given below.

Schemes 1, 2, 3, 4, 5, and 6 above summarize generic procedures that permit the preparation of a wide variety of the compounds of the present invention 2 through the ability to introduce numerous R substituents represented by Z°-Q wherein Z° is a single bond, a wide variety of amino substituting groups represented by B-, B-CH₂, B-CO, and B-SO₂, and a large number of amide forming Y groups at the carboxylic acid group in which E° is C(O)NH. Examples 1, 2, and 3 below shows the preparation of a compound wherein X°is hydrido although other substituents can be present at this position.

Example 1

Tirethylamine (3. m , 24.8 mmol) was added to a solution of the appropriate phenol (5.0 g, 20.7 mmol) and triflic anhydride (4.18 mL, 24.8 mmol) in dichloromethane at -10°C. After stirring at room temperature for 3 hours, the solution was acidified with 2N hydrochloric acid and extracted with dichloromethane. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford the crude product. The product was purified by column chromatography (15% ethyl acetate- hexane) to afford 5.53 g (72%) of a clear oil of product EX-1A; H NMR ppm: 3.78 (s, 3H), 3.87 (d, 2H), 3.96 (s, 3H), 7.27 (d, IH, J = 9.2 Hz), 7.95 (d, IH, J =

9.2 Hz); ⁹F NMR ppm: -73.89 (s, 3F); HPLC purity (retention time): >99% (3.62 min); HRMS calcd for C11H10O8N1F3 (M⁺ + NH₄) 391.0423, found

391.0396. EX-IB

The triflate compound EX-1A (5.53 g, 14.8 mmol) was added to a solution of tri-n-butylphenylstannane (5.8 mL, 17.7 mmol), lithium chloride (1.9 g, 44.8 mmol), and tetrakis(triphenylphosphine)palladium(0) (34.0 mg, 0.29 mmol) in 74 mL of anhydrous dioxane. The solution was heated to 85°C for 18 hours. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford the crude product. The product was purified by column chromatography (15% ethyl acetate-hexane) to afford 3.32 g (74%) of a white solid of product EX-IB; lH NMR ppm: 3.69 (s, 5H), 3.94 (s, 3H), 7.17 (d, IH, J = 8.3 Hz), 7.29 (m, 2H), 7.45 (m, 3H), 7.89 (d, IH, J = 8.3 Hz); HPLC purity (retention time): >99% (3.60 min); HRMS calcd for Cι₆Hi5θ5Ni

(M⁺ + NH₄) 319.1294, found 319.1312.

EX-1C

e

A catalytic amount of palladium on carbon (5%) in dioxane was added to the nitro compound EX- IB (3.3 g, 11.0 mmol) in a 1:1 mixture of methanol and dioxane. The mixture was hydrogenated on a Parr Hydrogenator (50 psi, room temperature) until hydrogen uptake stopped (4 hrs). The mixture was filtered through celite and the solvent was removed to afford the product. The product EX- 1C was not purified and carried on to the next step. HPLC purity (retention time): 96.5% (2.03 min). EX-ID

Sodium triacetoxyborohydride (9.3 g, 43.0 mmol) was added to a solution of the aniline EX-IC (2.99 g, 11.0 mmol), acetone (1.0 mL, 13.6 mmol), and a drop of acetic acid in a tetrahydrofuran-dichloromethane (1:1) solution. After stirring at room temperature for 14 hours, additional acetone (1.0 mL, 13.6 mmol) and acetic acid (excess) was added, and the solution stiπed at room temperature for 18 hours. The solution was diluted with ether and water. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford the crude product. The product was purified by column chromatography (15% ethyl acetate-hexane) to afford 3.55 g (100%) of a yellow oil of product EX- ID; *H NMR ppm: 1.24 (d, 6H), 3.59 (s, 3H), 3.62 (m, 2H), 3.72 (s, 3H), 4.09 (m, IH), 6.62 (d, IH, J = 8.3 Hz), 6.92 (d, IH, J = 8.3 Hz), 7.28 (m, 5H); HPLC purity (retention time): 97.5% (2.57 min).

EX-IE

Aqueous sodium hydroxide (10%) (7.6 mL, 19.0 mmol) was added to a solution of the methyl ester EX-ID (1.51 g, 4.81 mmol) in methanol and the resulting solution stiπed at 60°C for 3 hours. The solution was acidified with 2 N hydrochloric acid and extracted with diethyl ether. The solution was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford the crude product. The product was purified by column chromatography (40% ethyl acetate-hexane) to afford 0.44 g (31%) of a white solid of product EX- IE; ^lH NMR ppm: 1.25 (d, 6H), 3.62 (m, 3H), 3.75 (s, 3H), 6.50 (d, IH, J = 8.3 Hz), 6.94 (d, IH, J = 8.3 Hz), 7.27 (m, 5H); HPLC purity (retention time): >99% (2.11 min).

EX-1F

z

PS-carbodiimide (1.00 mmol/g) (2.8 g, 2.8 mmol) was added to a slurry of the acid EX- IE (0.42 g, 1.4 mmole), 1-hydroxybenzotriazole (0.19 mg, 1.4 mmol), the Cbz-amine (0.54 g, 1.6 mmol), and N-methylmorpholine (620 uL, 5.6 mmol) in a dichloromethane-dimethylformamide (3:1) solution, and the suspension was agitated for 18 hours. Upon completion of the reaction, the polyamine resin (2.81 mmol/g) (1.0 g, 2.8 mmol) and polymer-bound aldehyde (2.3 mmol/g) (1.0 g, 2.30 mmol) were added, and the suspension was agitated for 1 hour. The solution was filtered, and the polymer was rinsed with dimethylformamide and dichloromethane until no more UV activity was seen in the dichloromethane washing. The combined filtrate and washings were evaporated to afford the crude product. The product was purified by column chromatography (60% ethyl acetate-hexane), stuck to the column, and was washed off with 100% ethyl acetate to afford 0.73 g (92%) of a white solid of product EX-1F; H NMR ppm: 1.25 (d, 6H), 3.62 (m, 3H), 3.71 (s, 3H), 433 (d, 2H), 5.19 (s, 2H), 6.05 (bt, IH), 6.63 (d, 2H, J = 8.3 Hz), 6.93 (d, 2H, J = 8.3 Hz), 7.29 (m, 13H), 7.77 (d, 2H); HPLC purity (retention time): >99% (2.55 min). EX-IG

Boron tribromide 1M (2.7 mL, 2.7 mmol) was added to a solution of the ether EX- IF (0.50 g, 0.88 mmol) in dichloromethane at -10°C. The solution stirred at -10°C for 1.5 hours. The solution was quenched with water and evaporated to a minimal amount of solvent. The crude product mixture was purified directly by reverse-phase chromatography to afford a mixture of two products. Fraction one of reverse-phase chromatography afforded 0.22 g (60%) of a purple-white solid of product EX-IG; *H NMR ppm: 1.41 (d, 6H), 3.68 (s, 2H), 3.89 (m, IH), 4.28 (s, 2H), 6.97 (m, IH), 7.25-7.92 (m, 11H); HPLC purity (retention time): >99% (1.42 min).

A solution of potassium nitrosodisulfonate (Fremy's salt) (0.15 g, 0.56 mmol) in 5 mL of water was added to a solution of the phenol EX-IG (76.9 mg, 0.18 mmol) in 5 mL of dioxane. The solution stirred at room temperature for 2 hours (turning deep red-brown). The solvent was removed by evaporation to afford the crude product. The product was purified by reverse phase chromatography to afford 4.2 mg (54%) of a purple solid of product; HPLC purity (retention time): 85% (1.75 min).

Example 2

EX-2A

Sodium triacetoxyborohydride (2.8 g, 13.2 mmol) was added to a solution of the aniline prepared in Example 1 (EX-IC) (0.89 g, 3.3 mmol), phenylacetaldehyde (540 uL, 39.2 mmol), and a drop of acetic acid in a tetrahydrofuran-dichloromethane (1:1) solution. After stirring at room temperature for 2 hours, the solution was diluted with dichloromethane and water. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford the crude product. The product was purified by column chromatography (25% ethyl acetate-hexane) to afford 0.69 g

(56%) of a yellow oil of product EX-2A; H NMR ppm: 3.04 (t, 2H), 3.50 (t, 2H), 3.69 (s, 3H), 3.67 (s, 2H), 3.69 (s, 3H), 6.75 (d, IH, J = 8.3 Hz), 7.02 (d, IH, J = 8.3 Hz), 7.35 (m, 10H); HPLC purity (retention time): >99% (4.37 min); HRMS calcd for C24H25O3N1 (M⁺ + H) 376.1913, found 376.1872.

EX-2B

Aqueous sodium hydroxide (10%) (2.9 mL, 7.2 mmol) was added to a solution of the methyl ester EX-2A (0.69 g, 1.8 mmol) in methanol and the resulting solution stirred at 60°C for 5 hours. The solution was acidified with 2 N hydrochloric acid and extracted with diethyl ether. The solution was washed with brine, dried over magnesium sulfate, and filtered. The solvent was removed by evaporation to afford 0.66 g (100%) of an orange foam of product EX-2B; HPLC purity (retention time): 80% (3.83 min).

EX-2C

1-Hydroxybenzotriazole (247 mg, 1.8 mmol) was added to a slurry of the acid EX-2B (0.66 g, 1.83 mmole) and PS-carbodiimide (1.00 mmol/g) (3.6 g, 3.6 mmol) in a dichloromethane-dimethylformamide (3:1) solution. The suspension was agitated for 15 minutes. The Cbz-amine (0.70 g, 2.2 mmol) and N- methylmorpholine (1.0 mL, 9.0 mmol) was added and the suspension was agitated for 18 hours. Upon completion of the reaction, the polyamine resin (2.81 mmol/g) (1.0 g, 2.81 mmol) and polymer-bound aldehyde (2.3 mmol/g) (1.0 g, 2.30 mmol) were added and the suspension was agitated for 1 hour. The solution was filtered, and the polymer was rinsed with dimethylformamide and dichloromethane until no more UV activity was seen in the dichloromethane washing. The combined filtrate and washings were evaporated to afford the product. The product was purified by column chromatography (60% ethyl acetate-hexane) to afford 0.52 g (45%) of a white solid of product EX-2C; *H NMR ppm: 3.17 (m, 2H), 3.65 (m, 2H), 3.77 (s, 2H), 3.86 (s, 3H), 4.64 (d, 2H), 5.27 (bt, IH), 4.40 (s, 2H), 6.96 (d, IH), 7.11 (d, IH), 7.56 (m, 16H), 8.23 (m, 3H), 8.41 (bt, IH), 9.40 (bs, IH), 9.75 (bs, IH); HPLC purity (retention time): >99% (3.80 min); HRMS calcd for C39H38O4N4

(M⁺ + H) 627.2971, found 627.2918. EX-2D

Boron tribromide 1M (1.1 mL, 1.0 mmol) was added to a solution of the ether EX-2C (0.22 g, 0.36 mmol) in dichloromethane at -10°C. The solution stirred at -10°C for 3.5 hours. The solution was quenched with water and evaporated to a minimal amount of solvent. The crude product mixture was purified directly by reverse-phase chromatography to afford 0.10 g (60%) of a white solid of product EX-2D; *H NMR ppm: 3.12 (t, 2H), 3.66 (m, 4H), 4.51 (s, 2H), 6.96 (d, IH), 7.36 (m, 12H), 7.55 (d, 2H), 7.80 (d, 2H); HPLC purity (retention time): 92% (2.53 min); HRMS calcd for C30H30O2N4 (M⁺ + H) 479.2447, found

479.2446.

A solution of potassium nitrosodisulfonate (Fremy's salt) (0.15 g, 0.56 mmol) in 5 mL of water was added to a solution of the phenol EX- 2D (100 mg, 0.23 mmol) in 5 mL of THF. The solution stirred at room temperature for 2 hours (turning deep red-brown). The solvent was removed by evaporation to afford the crude product. The product was purified by reverse phase chromatography to afford 3.0 mg (2%) of a purple solid of product; HPLC purity (retention time): 89% (1.52 min).

Example 3

Using the process of Example 1 and tributyl 3-(2-trimethylsilylethoxy- carbonylamido)phenylstannane in place of tributylphenylstannane, the compound of Example 3 is prepared.

Using the examples and methods described herein previously, the following examples having a amidinoaralkyl or amidinoheteroaralkyl type Y group could be prepared:

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminoρhenyl]- 6- [N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl] jacetamide;

2- [2- [N-[ [4-aminoiminomethylphenyl]methyl]-3- [3-aminophenyl]-6- [N-ethyl-N-methylhydrazino]- 1 ,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-5- cUoro-6-[N,N-dimethylhydrazino]-l,4-benzoquinonyl]]acetamide;

2-[2-[N-[[ aminoiminomethylρhenyl]methyl]-3-[3-aminophenyI]- chloro-6-[N-ethyl-N-methylhydrazino]- 1 ,4-benzoquinonyl]]acetamide; 2-[2-[N-[[ aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]-

6-|TN[,N-dimethylhydrazino]-l,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]- 6- [N-ethyl-N-methylhydrazino]- 1 ,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoinώnometbylphenyl]methyl]-3-[3,5-diaminophenyl]- 5-chloro-6-[N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]- 5-chloro-6-[N-ethyl-N-methylhydrazino]-l,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4~aminoiminomethylphenyl]methyl]-3-[3-amino-5- carboxyphenyl]- 6-[N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl]]acetamide; 2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5- carboxyphenyl]-6-[N-ethyl-N-methylhydrazino]-l,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5- carboxyphenyl]-5-chloro-6- [N,N-dimethylhydrazino]- 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5- carboxyphenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]- 1 ,4- benzoquinonyl]]acetamide; 2-[2-[N-[[ aιrύnoiminomefhylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenylj- 6-[N,N-dimethylhydrazinol,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]-6-[N-ethyl-N-methylhydrazino]- 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]-5-chloro-6-[N,N-dimethylhydrazino]-l,4- benzoquinonyl]]acetamide;

2- [2- [N-[[4-aminoiminomethylphenyl]methyl]-33-amino-5-(N- benzylamidocarbonyl)phenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]-l,4- benzoquinonyl]]acetamide.

Using the examples and methods described herein previously, the following further examples having a amidinoaralkyl or amidinoheteroaralkyl type Y group could be prepared of the formula:

~ 0 wherein B, A, R , X , and Y are selected to form the following compounds:

R is 3-aminophenyl, B is phenyl, A is CH2, Y is 4-amidinobenzyl, and

X is chloro;

7 0

R is 3-aminoρhenyl, B is 3-chloroρhenyl, A is CH2CH2, Y is 4- amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is phenyl, A is CH2, Y is 4-amidinobenzyl, and

X is hydrido; 0

R is 3-aminophenyl, B is 2-imidazoyl, A is CH2CH2CH2, Y is 4- amidinobenzyl, and X is chloro; p

R is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH2CH2,

Y is 4-amidinobenzyl, and X is chloro; p R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is CH2CH2, Y is 4-amidinobenzyI, and X is chloro; p

R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is 3- chlorophenyl, A is CH2CH2, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is 3- chlorophenyl, A is CH2CH2, 1 is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2-trifluoromethylbenzyI)amidocarbonyl)- phenyl, B is

3-chlorophenyl, A is CH₂CH2, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 3,5-diaminophenyl, B is 3-chlorophenyl, A is QH^Q^Y is 4- amidinobenzyl, and X is chloro; R is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH2CH2, Y is

4-amidinobenzyl, and X is chloro; p

R is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH2CH2, x is 4-amidinobenzyl, and X is hydrido;

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is CH2CH2, Y is 4-amidinobenzyl, and X is hydrido; p

R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is 3- chlorophenyl, A is CH₂CH₂, 1 is 4-amidinobenzyl, and X is hydrido; p

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is 3- chlorophenyl, A is CH₂CH2, Y is 4-amidinobenzyl, and X is hydrido; p R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)- phenyl, B is

3-chlorophenyl, A is CH2CH2, Y is 4-amidinobenzyl, and X is hydrido; 9 0

R is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH2CH2, Y is 4- amidinobenzyl, and X is hydrido;

9 0

R is 3-amino- carboxyphenyl, B is 3-chlorophenyl, A is CH2CH2, Y is

4-amidinobenzyl, and is hydrido;

? 0 R is 3-aminophenyl, B is 2,2,2-trifϊuoroethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

? 0

R is 3-aminophenyl, B is (S)-2-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 5-amιno-2-fluorophenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

R 2 is 2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is ethyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro; R 2 is 3-aminophenyl, B is ethyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X is chloro;

? 0

R is 3-aminophenyl, B is 2-propenyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is isopropyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

? 0

R is 3-aminophenyl, B is 2-butyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro;

9 0 R is 3-aminophenyl, B is (R)-2-butyl, A is a bond, Y is 4-amidιnobenzyl, and X is chloro; 9 0

R is 3-aminophenyl, B is 2-proρynyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is 3-pentyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

2 0 R^ is 3-aminophenyl, B is hydrido, A is CH₂, Y is 4-amidinobenzyl, and

X is chloro;

R is 3-aminophenyl, B is ethyl, A is CH₂, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is 2-methypropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is 2-propyl, A is CH3CH, Y is 4-amidinobenzyl, and X is chloro;

9 0

R is 3-aminophenyl, B is propyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

2 0 R is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y is 4- amidinobenzyl, andX is chloro;

2 0

R is 3-aminophenyl, B is tert-butyl, A is a bond, Y is 4-amidinobenzyl, and X is hydrido;

2 0

R is 3-aminophenyl, B is tert-butyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

9 0

R is 3-aminophenyl, B is 3-hydroxypropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

9 0

R is 3-aminoρhenyl, B is 2-methylproρyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

9 0 R is 3-aminophenyl, B is butyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro; R 2 is 3-aminophenyl, B is l-methoxy-2-propyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is 2-methoxyethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is 2-propyl, A is a bond, Y is 5-amidino-2- thienylmethyl, and X is chloro;

R 2 is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

R 2 is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

R 2 is 3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is bromo; R 2 is 3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2

R is 3-amino-5-(N-benzyl-N-methylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p R is 3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; 2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl,

A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2

R is 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,

A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-armno-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p R^Δ is 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(3-ρyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(2-(4-methoxyρhenyl)ethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p R is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; 2

R is 3~amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2

R is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; R² is 3-amino-5-(N-(l ,2,3,4-tetrahydronaphth-2- ylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R 2 is 3-aminophenyl, B is 2-propyl, A is a bond, Y 0 is 4-amidino-3- fluorobenzyl, and X is hydrido;

2 0 R is 3-carboxyphenyl, B is 2-propyl, A is a bond, Y is 4-amidinobenzyl, and X is hydrido;

R 2 is 3-aminophenyl, B is 2-propyl, A is a bond, Y 0 is 4-amidino-3- fluorobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is (S)-2-butyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro; R 2"⁶ is 3 ,5-diaminophenyl, B is isopropyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzylbenzyl, and X is chloro;

2 0

R is 3, diaminophenyl, B is ethyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro;

2 0

R is 3,5-diaminophenyl, B is ethyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

R is 3-amino- carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is

4-amidinobenzyl, and X is chloro; R 2 is 3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y is 4- amidino-2-fluorobenzylbenzyl, and X is chloro;

R 2 is 3-amino- carboxyphenyl, B is ethyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-amino-Scarboxyphenyl, B is ethyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)ρhenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is (S)-2-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidino-2-fluorobenzylbenzyl, and X is chloro; p R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond, i is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond, i is 4-amidino-2-fluorobenzyl, and X is chloro;

9 o

R is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzylbenzyl, and X is hydrido;

R 2 is 3-aminophenyl, B is cyclopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X° is chloro;

9 0

R is 3-aminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X° is chloro;

2 0 R is 3-aminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; 2 0

R is 3-aminophenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X° is chloro;

2 0

R is 3-aminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; R 2 is 3-aminophenyl, B is cyclobutyl, A is a bond, Y 0 is 4-amidino-3- fluorobenzyl, and X° is chloro;

2 0

R is 3-aminophenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R 2 is 5-amino-2-thienyl, B is cyclobutyl, A is a bond, Y 0 is 4- amidinobenzyl, and X° is chloro;

2 0

R is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y is 4-amidinobenzyl, and X° is chloro;

2 0

R is 3-aminophenyl, B is 2-(2R)-bicyclo[2.2.1]-heptyl, A is a bond, Y is

4-amidinobenzyl, and X° is chloro; R 2 is 3-aminophenyl, B is cyclopentyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X° is chloro;

R is 3-aminophenyl, B is cyclohexyl, A is CH₂CH2, i is 4- amidinobenzyl, and X° is hydrido;

R is 3-aminophenyl, B is oxalan-2-yl, A is CH₂, i is 4-amidinobenzyl, and X° is chloro ;

2 0

R is 3-aminophenyl, B is 1-piperidinyl, A is CH₂CH2, Y is 4- amidinobenzyl, and X° is chloro;

R² is 3-aminophenyl, B is 1-pyπolidinyl, A is CH₂CH₂CH2, ϊ is 4- amidinobenzyl, and X° is chloro;

2 0 R is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; 2 0

R is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

2 0

R is 3 ,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido; R 2^Λ is 2-amino-6-carboxy-4-pyridyl, B is cyclobutyl, A is a bond, Y 0 is

4-amidinobenzyl, and X° is hydrido;

R 2 is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y 0

is 4-amidinobenzyl, and X° is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

R 2 i •s 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X° is chloro;

2 0

R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X° is chloro;

2 0 R is 3, diaminophenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X° is chloro;

2 0

R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

2 0

R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3- fluorobenzyl, and X° is chloro;

R 2 is 3,5-diaminophenyl, B is cyclopentyl, A is a bond, Y 0 is 4- amidinobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y is 4- amidinobenzyl, andX° is chloro;

2 o R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidino-2-fluorobenzyl, and X° is chloro; 2 0

R is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y is 4- amidino-2-fluorobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido; R 2 is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y 0 is 4- amidino-3-fluorobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclopentyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-benzylamιdocarbonyl)phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; p R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro; 2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2 R is 3-arnino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclopropyl, A is a bond, Y is amidino-2-fluorobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R is 3-arm^o-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; p

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro; p R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; p

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro; p

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; p

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro; and p

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro. Using the examples and methods described herein previously, the following

AT further a addddiittiioonnaall eexxaammpples having a guanidinoalkyl type Y group could be prepared of the formula:

wherein B, A, R ,X°, andY are selected to form the following compounds:

2 AT

R is 3-aminophenyl, B is phenyl, A is CH2CH2, Y is 5- guanidino- 1- oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

R is 3,5-diaminoρhenyl, B is phenyl, A is CH2CH2, 1 is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

R is 3-carboxy-5-aminophenyl, B is phenyl, A is CH2CH2, 1 is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is phenyl, A is

AT o

CH2CH2, Y is 5-guanidino- l-oxo-l-(2-thiazolyl)-2-pentyl, and X is chloro;

2 AT

R is 3,5-diaminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 AT

R is 3-carboxy- aminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is

AT o single bond, Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X is chloro;

2 AT

R is 3, diaminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; 2 AT

R is 3-carboxy-5-amιnophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is single bond, Y is 5-guanidino- 1-oxo- l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 AT R^A is 3-aminophenyl, B is phenyl, A is CH2CH2, Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, andX° is hydrido;

2 AT

R is 3,5-diaminophenyl, B is phenyl, A is CH2CH2, Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, andX° is hydrido;

2 AT

R is 3-carboxy-5-aminophenyl, B is phenyl, A is GH^QH^Y is 5- guanidino- 1 -oxo- l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is phenyl, A is

CH2CH2, 1 is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2 AT

R is 3,5-diaminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2 AT

R is 3-carboxy-5-aminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is

AT single bond, Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X^υ is hydrido;

2 AT R is 3,5-diaminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2 AT

R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido; and p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is

AT o single bond, Y is 5-guanidino- 1-oxo- l-(2-thiazolyl)-2-pentyl, and X is hydrido. Formula (I) compounds of this invention possessing hydroxyl, thiol, and amine functional groups can be converted to a wide variety derivatives. A hydroxyl group in the form of an alcohol or phenol can be readily converted to esters of carboxylic, sulfonic, carbamic, phosphonic, and phosphoric acids. Acylation to form a carboxylic acid ester is readily effected using a suitable acylating reagent such as an aliphatic acid anhydride or acid chloride. The corresponding aryl and heteroaryl acid anhydrides and acid chlorides can also be used. Such reactions are generally carried out using an amine catalyst such as pyridine in an inert solvent. Similarly, carbamic acid esters (urethanes) can be obtained by reacting a hydroxyl group with isocyanates and carbamoyl chlorides. Sulfonate, phosphonate, and phosphate esters can be prepared using the coπesponding acid chloride and similar reagents. Compounds of Formula (I) that have at least one thiol group present can be converted to the corresponding thioesters derivatives analogous to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of Formula (I) that have at least one primary or secondary amine group present can be converted to the coπesponding amide derivatives. Amides of carboxylic acids can be prepared using the appropriate acid chloride or anhydrides with reaction conditions analogous to those used with alcohols and phenols. Ureas of the coπesponding primary or secondary amine can be prepared using isocyanates directly and carbamoyl chlorides in the presence of an acid scavenger such as triethylamine or pyridine. Sulfonamides can be prepared from the coπesponding sulfonyl chloride in the presence of aqueous sodium hydroxide. Suitable procedures and methods for preparing these derivatives can be found in House's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The Systematic Identification of Organic Compounds, 5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons. Reagents of a wide variety that can be used to derivatize hydroxyl, thiol, and amines of compounds of Formula (I) are available from commercial sources or the references cited above, which are incorporated herein by reference.

Formula (I) compounds of this invention possessing hydroxyl, thiol, and amine functional groups can be alkylated to a wide variety derivatives. A hydroxyl group of compounds of Formula (I) can be readily converted to ethers. Alkylation to form an ether is readily effected using a suitable alkylating reagent such as an alkyl bromide, alkyl iodide or alkyl sulfonate. The coπesponding aralkyl, heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl, and heteroaralkyloxyalkyl bromides, iodides, and sulfonates can also be used. Such reactions are generally carried out using an alkoxide forming reagent such as sodium hydride, potassium t-butoxide, sodium amide, lithium amide, and n-butyl lithium using an inert polar solvent such as DMF, DMSO, THF, and similar, comparable solvents, amine catalyst such as pyridine in an inert solvent. Compounds of Formula (I) that have at least one thiol group present can be converted to the coπesponding thioether derivatives analogous to those of alcohols and phenols using the same reagents and comparable reaction conditions. Compounds of Formula (I) that have at least one primary, secondary or tertiary amine group present can be converted to the coπesponding quaternary ammonium derivatives. Quaternary ammonium derivatives can be prepared using the appropriate bromides, iodides, and sulfonates analogous to those used with alcohols and phenols. Conditions involve reaction of the amine by warming it with the alkylating reagent with a stoichiometric amount of the amine (i.e., one equivalent with a tertiary amine, two with a secondary, and three with a primary). With primary and secondary amines, two and one equivalents, respectively, of an acid scavenger are used concuπently. Tertiary amines can be prepared from the coπesponding primary or secondary amine by reductive alkylation with aldehydes and ketones using reduction methods. Suitable procedures and methods for preparing these derivatives can be found in House's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner, Fuson, and Curtin in The Systematic Identification of Organic Compounds, 5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents for Organic Synthesis, Volume 1, John Wiley & Sons. Perfluoroalkyl derivatives can be prepared as described by DesMarteau in J. Chem. Soc. Chem. Commun. 2241 (1998). Reagents of a wide variety that can be used to derivatize hydroxyl, thiol, and amines of compounds of Formula (I) are available from commercial sources or the references cited above, which are incorporated herein by reference.

The biological activity of the compounds of Examples 1 and 2 and

Schemes 1, 2, 3, 4, 5, and 6 can be evaluated using bioassay procedures below.

Assays for Biological Activity

TF-VIIa Assay

In this assay 100 nM recombinant soluble tissue factor and 2nM recombinant human factor Vila are added to a 96-well assay plate containing 0.4 mM of the substrate, N-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline and either inhibitor or buffer (5 mM CaCl₂,50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in a final volume of 100 ul is measured immediately at 405 nm to determine background absorbance. The plate is incubated at room temperature for 60 min, at which time the rate of hydrolysis of the substrate is measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of TF-VIIa activity is calculated from OD_405nm value from the experimental and control sample.

Xa Assay

0.3 nM human factor Xa and 0.15 mM N-α-Benzyloxycarbonyl-D-arginyl-L- glycyl-L-arginine-p-nitroaniline-dihydrochloride (S-2765) are added to a 96-well assay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in a final volume of 100 ul is measured immediately at 405 nm to determine background absorbance. The plate is incubated at room temperature for 60 min, at which time the rate of hydrolysis of the substrate is measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of Xa activity is calculated from OD_405nm value from the experimental and control sample.

Thrombin Assay

0.28 nM human thrombin and 0.06 mM H-D-Phenylalanyl-L-pipecolyl-L-arginine- p-nitroaniline dihydrochloride are added to a 96-well assay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in a final volume of 100 ul is measured immediately at 405 nm to determine background absorbance. The plate is incubated at room temperature for 60 min, at which time the rate of hydrolysis of the substrate is measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of thrombin activity is calculated from OD_405nm value from the experimental and control sample.

Trypsin Assay 5 ug/ml trypsin, type IX from porcine pancreas and 0.375 mM N-α-Benzoyl-L- arginine-p-nitroanilide (L-BAPNA) are added to a 96-well assay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reactions, in a final volume of 100 ul are measured immediately at 405 nm to determine background absorbance. The plate is incubated at room temperature for 60 min, at which time the rate of hydrolysis of the substrate is measured by monitoring the reaction at 405 nm for the release of p-nitroaniline. Percent inhibition of trypsin activity is calculated from OD_405nm value from the experimental and control sample.

Recombinant soluble TF, consisting of amino acids 1-219 of the mature protein sequence was expressed in E. coli and purified using a Mono Q Sepharose FPLC. Recombinant human Vila was purchased from American Diagnostica, Greenwich CT and chromogenic substrate N-Methylsulfonyl-D- phe-gly-arg-p-nitroaniline was prepared by American Peptide Company, Inc., Sunnyvale, CA. Factor Xa was obtained from Enzyme Research Laboratories, South Bend IN, thrombin from Calbiochem, La Jolla, CA, and trypsin and L- BAPNA from Sigma, St. Louis MO. The chromogenic substrates S-2765 and S-2238 were purchased from Chromogenix, Sweden.

The biological activity of the products of Examples 1 and 2 are summarized below in Table 1.

Table 1. Inhibitory Activity of Substituted Quinones toward Factor Xa, TF-VIIA, Thrombin II, and Trypsin II.

Claims

What we claim is:

1. A compound having the Formula (I):

or a pharmaceutically acceptable salt thereof, wherein; B is formula (V):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 2 1 1 2 1 2 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K

1 2 1 1 must be a covalent bond when two of D , D ,J , J andK are O and S, and

, , ._τ.1 _τ.2 _τl 2 _ΔτΛ _τ ., , . , >2 no more than four of D ,D ,J ,J andK are N with the proviso that R ,

33 34 35 36

R ,R ,R ,andR are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

32 33 34 35 36 b

R ,R ,R ,R ,andR are independently selected to be Q ; „9 10 11 n 13 „16 11 18 19 32 33 34 35 _J R , R , R , R , R , R , R , R , R , R , R , R , R , and

36 R are independently selected from the group consisting of hydndo, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl ; τ,32 _Λ 33 33 , _π34 34 _J 35 ₃ „35 _J 36 R and R , R and R , R and R , an R and R substituent pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than

32 33 33 34 34 one of the group consisting of spacer pairs R and R , R and R , R

35 35 36 and R , an R and R are used at the same time;

B is formula (VI):

3 4 3 wherein DD~ ,,DD ^' ,,r . J ,, and J ^' are independently selected from the group

3 4 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no

3 4 3 4 1 2 1 more than one of D , D , J , and J is S, and no more than three of D , D , J ,

, _τ2 _τ . , , . , „32 „33 34 , 35 and J are N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

B is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R32, R33, R34, R35, and R^g,

B is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R γ , a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ, a ring carbon or nitrogen atom adjacent to the R_j3 position and two atoms

from the point of attachment may be substituted with Rχ2_> ^a "ng carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with γ _j , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j2 position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34; τ,9 _{1 T}, 10 „10 _{J ¥},ll „ll _{Δ r}Λ2 _{1 ¥}_ 12 13 R and R , R and R , R and R , and R and R spacer pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group

. . . 9 10 10 1 1 11 12 12 consisting of spacer pairs R and R , R and R , R and R , and R

13 and R is used at the same time;

A is selected from the group consisting of single covalent bond,

(W⁷)_rτ-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W⁷)_rr wherein π is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O,

C(O)N(R^?), C(S)N(R⁷), (R^?)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, Se(O), Se(O)₂, Se(O)₂N(R⁷), (R^?)NSe(O)₂, P(O)(R⁸),

N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), C(NR^?)N(R⁷), (R⁷)NC(NR^?), and N(R^?);

7 8 R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, alkylamino, arylthio, arylamino, acyl, aroyl, heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl, , aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, heteroaryl, heteroaryloxy, heteroarylamino, heteroaralkyl, heteroaralkyloxy, heteroaralkylamino, and heteroaryloxyalkyl;

„14 15 37 38 39 40 41 _J 42 . _{J Λ} , R , R , R , R , R ,R , R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl, carboaralkoxy, trialkylsilyl, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl ;

14 14

R and R , when bonded to different carbons, are taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

14 15

R and R , when bonded to different carbons, are taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of a cycloalkyl ring having from 5 through 8 contiguous members, a cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

15 15

R and R , when bonded to different carbons, are taken together to form a group selected from the group consisting of covalent bond, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

14 15

R and R , when bonded to the same carbon, are taken together to form a group selected from a group consisting of oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer selected to form a ring selected from the group consisting of cycloalkyl ring having from 5 through 8 contiguous members, cycloalkenyl ring having from 5 through 8 contiguous members, and a heterocyclyl having from 5 through 8 contiguous members;

Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

5 8 39 40

S(O), S(O)₂, ON(R ), P(O)(R ), and CR R ;

R is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio, arylthio, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, and dialkoxyphosphonoalkyl;

X and R are independently selected from the group consisting of Z -

Q, hydrido, alkyl, alkenyl, and halo;

0 2

X and R are independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono;

X and R are taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members; o 39

X and R are taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members; o 40

X and R are taken together to form a spacer pair wherein the spacer pair forms a linear spacer moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members; X is selected to form a linear moiety having from 2 through 5

39 40 contiguous atoms linked to the points of bonding of both R and R to form a heterocyclyl ring having from 5 through 8 contiguous members;

R and R , R and R , R and R , and R and R spacer pairs are independently selected to form spacer pairs wherein a spacer pair is taken together to form a linear moiety having from 2 through 5 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having from 5 through 8 contiguous members with the proviso that no more than one of the group of spacer pairs consisting of R and

4a 2 4b 2 14 9 15

R , R and R , R and R , and R and R is used at the same time;

2 R is independently selected to form a linear moiety having from 2

4a through 5 contiguous atoms linked to the points of bonding of both R and

4b R to form a heterocyclyl ring having from 5 through 8 contiguous members;

Z is selected from the group consisting of covalent single bond,

41 42 41 (CR R )„ wherein q is an integer selected from 1 through 6, (CH(R ))„- o 42 W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O, S, C(O), C(S),

41 41 41

C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ), (R )NC(O), C(S)N(R ),

41 41 41 41 41

(R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ), (R )NC(S)S,

41 41 41 41

SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

42 41 41 42 42 41 N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ),

(R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹), N(R⁴¹)S(O)₂, Se, Se(O), 41 41 8 7 8

Se(O)₂,Se(O)₂N(R ),N(R )Se(O)₂,P(O)(R ),N(R )P(O)(R ),

8 7 41 41 28 29 41 2

P(O)(R )N(R ),N(R ),ON(R ),andSiR R ,and(CH(R ))_e-W -

42 (CH(R ) wherein e and h are integers independently selected from 0

2 41 42 through 2 and W^{^} is selected from the group consisting of CR =CR ,

41 42 CR R =C; vinylidene), and ethynylidene (C=C; 1,2-ethynyl), with the

41 42 provisos that R and R are selected from other than halo and cyano when o directly bonded to N and Z is directly bonded to the quinone ring;

Q is formula (II):

1 2 1 2 1 wherein D , D ,J ,J and are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 1 1 2 1 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K

1 2 1 2 1 must be a covalent bond when two of D , D , J , J and K are O and S, and

1 2 1 2 1 9 no more than four of D , D ,J , J andK are N, with the proviso that R ,

„10 11 „12 13 , . , , , , , . . ,

R ,R ,R ,andR are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; Q is formula (III):

_^3 4 . A wherein DD~,, DD ^',, JJ~,, a; nd J ^' are independently selected from the group

3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no

3 4 3 4 1 2 1 more than one of D , D , J~\ and J is S, and no more than three of D , D , J ,

2 9 10 11 12 and J are N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

. Q is selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxy alkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl; K is (CR j )_n wherein n is an integer selected from 1 through 4;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfmyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, and aralkylsulfonylalkyl;

4a 4b

R and R , when bonded to the same carbon, are taken together to form a group selected from the group consisting of oxo, thiono, and a linear spacer moiety having from 2 through 7 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkyl ring having 3 through 8 contiguous members, a cycloalkenyl ring having 5 through 8 contiguous members, and a heterocyclyl ring having 5 through 8 contiguous members; E is E , when K is (CR R )_n, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R⁷), (R^?)NC(S), OC(O)N(R^?),

(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R^?), (R⁷)NC(O)S,

OC(S)N(R^?), (R^?)NC(S)O, N(R⁸)C(O)N(R^?), (R⁷)NC(O)N(R⁸),

N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R^?)S(O)₂,

S(O)₂N(R⁷)C(O), C(O)N(R⁷)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R^?),

N(R⁷)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R^?), N(R^?), ON(R^?),

28 29 4a 4b 4a 4b

SiR R , CR =CR , ethynylidene (C≡C; 1,2-ethynyl), and C=CR R ;

14 K is (CH(R )) -T wherein j is selected from a integer from 0 through 3 and T is selected from the group consisting of single covalent bond, O, S, and

7 14

N(R ) with the proviso that (CH(R )); is bonded to the quinone ring; o 2 14 2

E is E , when K is (CH(R ))j-T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), (R⁷)NC(O)O,

(R⁷)NC(S)S, (R⁷)NC(O)S, (R^?)NC(S)O, N(R⁸)C(O)N(R^?),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R^?)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R⁷), N(R^?)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, Se(O),

Se(O)₂, Se(O)₂N(R⁷), N(R^?)Se(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸),

P(O)(R⁸)N(R⁷), and N(R^?); K is G-(CH(R ))_]j wherein k is selected from an integer from 1

7 through 3 and G is selected from the group consisting of O, S, and N(R ) with

the proviso that R is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1; E is E , when K is G-(CH(R ) , wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R^?), (R^?)NC(S),

OC(O)N(R^?), (R⁷)NC(O)O, SC(S)N(R^?), (R^?)NC(S)S, SC(O)N(R⁷),

(R^?)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R^?)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R^?), N(R^?)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R^?), N(R^?)Se(O)₂,

8 7 8 8 7 7 7 28 29

P(O)(R ), N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), SiR R ,

4a 4b 4a_4b

CR =CR , ethynylidene (CsC; l,2-ethynyl), and C=CR II ;

Y° is formula (IV):

wherein are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one is a covalent bond, K is independently selected from the group

+ 5 6 5 6 consisting of C, and N , no more than one of D , D , J , and J is O, no more than one of D , D , J , and J is S, one of D , D , J , and J must be a

covalent bond when two of D , D , J , and J are O and S, no more than three

5 6 5 6 2 + 5 6 of D , D , J , and J are N when K is N , and no more than four of D , D ,

5 6 2 16 17 18

J , and J are N when K is carbon with the provisos that R , R , R , and

19 R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

16 17

R and R are independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl;

R and R are independently taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl; b 20 21 ₊ 20 21 22 Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,

20 aminoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22 R , and R is hydroxy, alkoxy, alkylamino, ammo, and dialkylamino and that

20 21 22

R , R , and R must be other than be hydroxy, alkoxy, alkylamino, amino,

2 + and dialkylamino when K is N ; 20 21 20 22 21 22

R andR ,R andR ,andR andR pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 4 through 7 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having 5 through 8 contiguous members with the proviso that no more than one of the

20 21 20 22 21 22 group consisting of spacer pairs R and R , R and R , and R and R is used at the same time; b 26 23 24

Q is selected from the group consisting of N(R )SO₂N(R )(R ),

N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵

23 24 26 with the proviso that no more than one of R ,R ,andR are hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the group consisting

23 24 26 ofR ,R ,andR are bonded to the same atom;

Q is selected from the group consisting of dialkylsulfonium,

25 O^ OΔ. f 25 OΔ. trialkylphosphonium, C(NR )NR R ,N(R )C(NR )N(R )(R ),

^Λ ^ ^A /^ ^* 'ζ N(R )C(O)N(R )(R ),N(R )C(S)N(R )(R ),C(NR )OR ,

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

N(R²⁶)N(R²⁶)C(NR²⁵)N( ²³)( ²⁴),N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),

25 5 23 24 23 24

C(NR )SR ,C(O)NR R ,andC(O)NR R with the provisos that no 2-1 Of more than one of R ,R ,an R is hydroxy, alkoxy, alkylamino, amino, or

23 24 26 dialkylamino when two of the group consisting of R ,R ,andR are

bonded to the same atom and that said Q group is bonded directly to a carbon atom;

„23 „24 25 , 26 . _J , , ,

R ,R ,R ,andR are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl; 23 24

R and R are taken together to form a linear spacer moiety having from 4 through 7 contiguous atoms connecting the points of bonding to form a heterocyclyl ring having 5 through 8 contiguous members;

23 _J 25 „24 _J 25 25 _J 26 24 _J 26 _, 23 R and R , R and R , R and R , R and R , and R

26 and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of 1,2-disubstituted radicals consisting of a cycloalkyl radical, a cycloalkenyl radical wherein cycloalkyl and cycloalkenyl radicals are substituted with one or

30 31 more groups selected from R and R , an aryl radical, an heteroaryl radical, a saturated heterocyclic radical and a partially saturated heterocyclic radical wherein

28 32 said 1,2-substitutents are independently selected from C=O, C=S, C(R )R ,

S(O), S(O)₂, OP(OR³¹)R³°, P(O)R³⁰, P(S)R³⁰ and Si(R²⁸)R²⁹;

23 25 24 25 25 26 24 26 23 26

R and R , R and R , R and R , R and R , and R and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group of radicals consisting of 1,2-disubstituted alkylene radicals and 1,2-disubstituted alkenylene radical wherein said 1,2-substitutents are independently selected from C=O, C=S, C(R²⁸)R²⁹, S(O), S(O)₂, OP(OR^{3 30}, P(O)R³⁰, P(S)R³⁰, and

28 29 Si(R )R and said alkylene and alkenylene radical are substituted with one or

30 31 more R or R substituents;

^23 _Λ „25 24 _J „25 25 , 26 „24 _J 26 , 23 _J 26 R and R , R and R , R and R , R and R , and R and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together from the points of bonding of selected spacer pair members to form the group L-U-V wherein L, U, and V are independently selected from the group consisting of O, S, C(O), C(S), C(J_H)₂ S(O), SO₂, OP(OR³¹)R³⁰, P(O)R³°, P(S)R³⁰, C(R³⁰)R³¹, C=C(R³⁰)R³¹, (O)₂POP(O)₂, R³⁰(O)POP(O)R³⁰, Si(R²⁹)R²⁸, Si(R²⁹)R²⁸Si(R²⁹)R²⁸, Si(R²⁹)R²⁸OSi(R²⁹)R²⁸,

(R²⁸)R²⁹COC(R²⁸)R²⁹, (R²⁸)R²⁹CSC(R²⁸)R²⁹, C(O)C(R³⁰)=C(R³¹),

30 31 30 31 30 31

C(S)C(R )=C(R ), S(O)C(R )=C(R ), SO₂C(R )=C(R ),

PR³⁰C(R³⁰)=C(R³¹), P(O)R³⁰C(R³⁰)=C(R³¹), P(S)R³⁰C(R³⁰)=C(R³¹), DC(R³°)(R³¹ )D, OP(OR³ )R³⁰, P(O)R³⁰, P(S)R³⁰, Si(R²⁸)R²⁹ and N(R³°), and a covalent bond with the proviso that no more than any two of L, U and V are simultaneously covalent bonds and the heterocyclyl comprised of by L, U, and V has from 5 through 10 contiguous member;

D is selected from the group consisting of oxygen, C=O, C=S, and S(O)_m wherein m is an integer selected from 0 through 2;

27 27 J_H is independently selected from the group consisting of OR , SR and

N(R²⁰)R²¹;

27 R is selected from the group consisting of hydrido, alkyl, alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryloxy alkyl, heteroaryl, heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsulfonylalkyl ;

28 29

R and R are independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl, perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl, heteroaryl thioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyi, carboalkoxyaikyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl, carboxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyl and diaralkoxyphosphonoalkyl;

R and R are taken together to form a linear moiety spacer having from

2 through 7 contiguous atoms and forming a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

30 31

R and R are independently selected from hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloaralkylsulfinylalkyl, aralkylsulfonylalkyl, cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyi, carboalkoxyaikyl, dicarboalkoxyalkyl, cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, phosphonoalkyl, dialkoxyphosphonoalkoxy, diaralkoxyphosphonoalkoxy, phosphonoalkoxy, dialkoxyphosphonoalkylamino, diaralkoxyphosphonoalkylamino, phosphonoalkylamino, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, sulfonylalkyl, alkoxysulfonylalkyl, aralkoxysulfonylalkyl, alkoxysulfonylalkoxy, aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino, aralkoxysulfonylalkylamino, and sulfonylalkylamino; 30 31

R and R are taken to form a linear moiety spacer group having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members; g

Q is selected from the group consisting of a single covalent bond,

(CR R )tø-(W )_az wherein az is an integer selected from 0 through 1, b is an integer selected from 1 through 4, and W is selected from the group consisting

14 of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R ),

(R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), SC(S)N(R¹⁴),

14 14 15 14 14 15

SC(O)N(R ), OC(S)N(R ), N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 17 14 8 N(R )S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R ), N(R )Se(O)₂, P(O)(R ),

7 8 8 7 14 14 28 29

N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), and SiR R ,

14 1 15 (CH(R ))_C-W -(CH(R ))_jj wherein c and d are integers independently

selected from 1 through 4, and W is selected from the group consisting of O,

S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R^M)NC(O),

C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴),

(R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S, OC(S)N(R¹⁴), (R¹⁴)NC(S)O,

15 14 14 15 15 14 N(R )C(O)N(R ),(R )NC(O)N(R ),N(R )C(S)N(R ),

14 15 14 14

(R )NC(S)N(R ),S(O),S(O)₂,S(O)₂N(R ),N(R )S(O)₂, Se, Se(O),

Se(O)₂, Se(O)₂N(R¹⁴), N(R¹⁴)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),

8 7 14 14 28 29 14 2 P(O)(R )N(R ),N(R ),ON(R ), SiR R ,and(CH(R ))_e-W - 15 (CH(R ))_j1 wherein e and h are integers independently selected from 0

2 4a 4b through 2 and W^{^} is selected from the group consisting of CR =CR ,

4a 4b 14 ethynylidene (C≡C; 1,2-ethynyl), and C=CR R with the provisos that R

and R are selected from other than halo and cyano when directly bonded to

37 38 14 14 n N and that (CR R )_b, (CH(R ))_C, (CH(R ))_e and are bonded to E ; 0 b ss ss i is Q -Q wherein Q is selected from the group consisting of

37 38 14

(CR R )f wherein f is an integer selected from 1 through 6, (CH(R ))_c-

W -(CH(R ))_(j wherein c and d are integers independently selected from 1

1 1 through 4, and W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,

14 14 14 14 14

C(O)N(R ), (R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ),

14 14 14 14 14

(R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S,

14 14 15 14 14 15

OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁴), N(R¹⁴)Se(O)₂, P(O)(R⁸),

N(R^?)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R ), SiR²⁸R²⁹, and

14 2 15

(CH(R ))_e-W -(CH(R ))_n wherein e and h are integers independently

selected from 0 through 2 and w is selected from the group consisting of

4a 4b 4a 4b

CR =CR , ethynylidene (C^C; 1,2-ethynyl), and C=CR R with the

14 15 provisos that R and R are selected from other than halo and cyano when

37 38 15 15 directly bonded to N and that (CR R )_f, (CH(R ))_c, and (CH(R ))_e are bonded to E ; Y is Q -Q wherein Q is (CH(R ))_r-W , r is an integer selected

3 from 1 through 3, and W is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, l,3-cyclopentyl, 2,3- morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4- morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2 -piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piρeridinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3- pyπolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidiny], 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4- pyranyl, 4H-2,5-ρyranyl, 2H-ρyran-2-one-3,4-yl, 2H-ρyran-2-one-4,5-yl, 4H- pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahy dropyranyl, 2,6-tetrahydroρyranyl, 3 ,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the proviso that (CH(R ))_r

is bonded to E and Q is bonded to lowest numbered substituent position of

each W ;

ϊ is Q -Q wherein Q is (CH(R ))_r-W , r is an integer

4 selected from 1 through 3, and W is selected from the group consisting of 1,2- cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6- morpholinyl, 3,4-morpholinyl, 3,5-mo holinyl, 1,2-piρerazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1 ,3-piperidinyl, 1 ,4-piperidinyl, 23-piperidinyl, 2,4-ρiperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3-pyrrolidinyl, 2,3-pyπolidinyl, 2,4-pyrrolidinyl, 2,5-pyπolidinyl, 3,4- pyπolidinyl, 2H-2,3-pyranyl, 2H-2,4~pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-ρyranyl, 2H-ρyran-2-one-3,4-yl, 2H-pyran-2-one-4,5- yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahydroρyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the provisos that (CH(R ))_r

is bonded to is bonded to highest number substituent position of

4 each W ;

Y is Q -Q wherein Q is (CH(R ))_r- W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1 ,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyi, 2,4-naρhthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinoMnyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3 ,5-isoquinolinyl, 3 ,6-isoquinolinyl, 3 ,7-isoquinolinyl, 3 ,8- isoquinolinyl, 4, isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

_r o W and that (CH(R ))_r is bonded to E ; i is Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,Sindazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naρhthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyI, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E ;

37 37

R and R , when bonded to different carbons, are taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members; 37 38

R and R , when bonded to different carbons, are taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

38 38

R and R , when bonded to different carbons, are taken together to form a linear moiety spacer having from 1 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

37 38

R and R , when bonded to the same carbon, are taken together to form a group selected from a group consisting of oxo, thiono, alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members;

39 40 R and R , when bonded to the same carbon, are taken together to

5 form a group selected from a group consisting of oxo, thiono, R -N, alkylene, haloalkylene, and a linear moiety spacer having from 2 through 7 contiguous atoms to form a ring selected from the group consisting of a cycloalkyl ring having from 3 through 8 contiguous members, a cycloalkenyl ring having from 3 through 8 contiguous members, and a heterocyclyl ring having from 3 through 8 contiguous members.

2. The compound as recited in Claim 1 or a pharmaceutically acceptable salt thereof, wherein; B is formula (V):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 1 1 2 1 2 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K

1 2 1 2 1 must be a covalent bond when two of D , D ,J , J andK are O and S, and

1 2 1 1 32 no more than four of D , D , J , J and K are N with the proviso that R ,

33 34 35 36

R ,R ,R ,andR are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

32 33 34 35 36 b

R ,R ,R ,R ,andR are independently selected to be Q ;

9 10 11 12 13 16 17 18 19 32 33 34 35 R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,R ,and

36 R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyaikyl, carboalkoxy alkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl ;

32 33 33 34 34 35 35 36

R and R , R and R , R and R , and R and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group 32 33 33 34 34 35 35 consisting of spacer pairs R and R , R and R , R and R , and R

36 and R is used at the same time;

B is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R3₂, R33, R34, R35, and R^ ',

B is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R₁ , a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ, a ring carbon or nitrogen atom adjacent to the R₁3 position and two atoms

from the point of attachment may be substituted with R_j2, a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_j 2 , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34;

_«9 _{J T}J0 10 11 „11 12 _{J T},12 _{J n} 13 . R and R , R and R , R and R , andR and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 3 through 6 contiguous atoms connecting the points of bonding of said spacer pair members to form a ring selected from the group consisting of a cycloalkenyl ring having 5 through 8 contiguous members, a partially saturated heterocyclyl ring having 5 through 8 contiguous members, a heteroaryl ring having 5 through 6 contiguous members, and an aryl with the proviso that no more than one of the group

9 10 10 11 11 12 12 consisting of spacer pairs R and R , R and R , R and R , and R

and R is used at the same time;

A is selected from the group consisting of single covalent bond, (W⁷)_rr-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W⁷)_rr wherein π is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O,

C(O)N(R⁷), C(S)N(R⁷), (R^?)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, P(O)(R⁸), N(R^?)P(O)(R⁸), P(O)(R⁸)N(R^?), C(NR^?)N(R⁷),

(R⁷)NC(NR⁷), and N(R^?);

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;

14 15 37 8

R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

5 Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

5 8 39 40 S(O), S(O)₂, ON(R ), P(O)(R ), and CR R ;

R is selected from the group consisting of hydrido, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, and heteroaroyl; 39 40

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy, carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

X and R are independently selected from the group consisting of Z -

Q, hydrido, alkyl, alkenyl, and halo;

0

X and R are independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono;

Z is selected from the group consisting of covalent single bond,

41 42 41 (CR R )q wherein q is an integer selected from 1 through 6, (CH(R ))_g- o 42 W -(CH(R ))p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O, S, C(O), C(S),

C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹),

41 41 41 41 41

(R )NC(S), OC(O)N(R ), (R )NC(O)O, SC(S)N(R ), (R )NC(S)S,

41 41 41 41

SC(O)N(R ), (R )NC(O)S, OC(S)N(R ), (R )NC(S)O,

42 41 41 42 42 41 N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ),

41 42 41 41 8

(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ), N(R )S(O)₂, P(O)(R ),

7 8 8 7 41 41 41 2

N(R )P(O)(R ), P(O)(R )N(R ), N(R ), ON(R ), and (CH(R ))_e-W -

42 (CH(R ))_jj wherein e and h are integers independently selected from 0 2 41 42 through 2 and W^{^} is selected from the group consisting of CR =CR ,

41 42 CR R =C; vinylidene), and ethynylidene (C≡ ; 1,2-ethynyl), with the 41 42 provisos that R and R are selected from other than halo and cyano when directly bonded to N and Z is directly bonded to the quinone ring;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl, aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfonyl, and aralkylsulfonylalkyl; Q is formula (II):

1 2 1 2 1 wherein D ,,DD,,JJ ,,Γ J and ^*-K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D ,D ,J ,J andK isO,

1 2 1 2 1 1 2 1 2 1 no more than one of D ,D ,J ,J andK is S, one of D ,D ,J ,J andK

1 2 1 2 1 must be a covalent bond when two of D , D ,J , J andK are O and S, and

1 2 1 2 1 9 no more than four of D , D , J , J and K are N, with the proviso that R ,

10 11 12 13

R ,R ,R ,andR are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitiogen, the divalent nature of sulfur, and the divalent nature of oxygen; Q is formula (III):

,3 J . A wherein D~, D , J~, and J ^" are independently selected from the group

3 4 3 4 consisting of C, N, O, and S, no more than one of D , D , J , and J is O, no

3 4 3 4 1 2 1 more than one of D , D , J , and J is S, and no more than three of D , D , J ,

2 9 10 11 12 an J are N with the proviso that R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

Q is selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl;

4a 4b K is (CR R )_n wherein n is an integer selected from 1 through 2;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, alkoxyalkyl, haloalkyl, haloalkenyl, and cyanoalkyl;

4a 4b

R and R , when bonded to the same carbon, are taken together to form a group selected from the group consisting of oxo, and a linear spacer moiety having from 2 through 7 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkyl ring having 3 through 8 contiguous members, a cycloalkenyl ring having 5 through 8 contiguous members, and a heterocyclyl ring having 5 through 8 contiguous members;

E is E , when K is (CR R )_n, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), OC(O)N(R^?),

(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R^?), (R⁷)NC(O)S,

OC(S)N(R⁷), (R^?)NC(S)O, N(R⁸)C(O)N(R⁷), (R^?)NC(O)N(R⁸),

N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R^?), N(R^?)S(O)₂,

S(O)₂N(R⁷)C(O), C(O)N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),

P(O)(R⁸)N(R⁷), N(R^?), ON(R⁷), CR^4a=CR^4b, ethynylidene (C≡C; 1,2-

4a 4b ethynyl), and C=CR R ;

14 K is (CH(R )):-T wherein j is selected from a integer from 0 through

2 and T is selected from the group consisting of single covalent bond, O, S, and

7 14

N(R ) with the proviso that (CH(R ))j is bonded to the quinone ring; o 2 14 2 E is E , when K is (CH(R ));-T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R⁷), (R^?)NC(S), (R^?)NC(O)O,

(R⁷)NC(S)S, (R^?)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R^?), N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, P(O)(R⁸),

N(R^?)P(O)(R⁸), P(O)(R⁸)N(R⁷), and N(R^?);

K is G-(CH(R ))ι, wherein k is selected from an integer from 1

7 through 2 and G is selected from the group consisting of O, S, and N(R ) with the proviso that R is other than hydroxy, cyano, halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1;

E is E , when K is G-(CH(R ^ wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R^?), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S),

OC(O)N(R⁷), (R^?)NC(O)O, SC(S)N(R⁷), (R^?)NC(S)S, SC(O)N(R⁷),

(R^?)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R⁷), N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷),

N(R^?), ON(R^?), CR^CR⁴¹⁵, ethynylidene (G≡C; 1 ,2-ethynyl), and

4a 4b C=CR R ;

Y° is formula (IV):

5 6 5 f wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one is a covalent bond, K is independently selected from the group

consisting of C, and N , no more than one of D , D , J , and J is O, no more

than one of D , D , J , and J is S, one of D , D , J , and J must be a

5 6 5 6 covalent bond when two of D , D , J , andJ are O and S, no more than three 5 6 5 6 2 + 5 6 of D , D , J , and J are N when K is N , and no more than four of D , D , r Λ f Λ H Λ 5Z.

J , and J are N when K is carbon with the provisos that R , R , R , and

19 R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

16 17

R and R are taken together to form a linear moiety spacer having from 3 through 6 contiguous atoms connected to form a ring selected from the group consisting of a cycloalkenyl ring having from 5 through 8 contiguous members, a partially saturated heterocyclyl ring having from 5 through 8 contiguous members, a heteroaryl having from 5 through 6 contiguous members, and an aryl; b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,

20 ammoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R is hydroxy, alkoxy, alkylamino, am o, and dialkylamino and that

20 21 22

R , R , and R must be other than be hydroxy, alkoxy, alkylamino, amino,

2 + and dialkylamino when K is N ;

20 21 20 22 21 22 R and R , R and R , and R and R pairs are independently selected to form a spacer pair wherein a spacer pair is taken together to form a linear moiety having from 4 through 7 contiguous atoms connecting the points of bonding of said spacer pair members to form a heterocyclyl ring having 5 through 8 contiguous members with the proviso that no more than one of the

20 21 20 22 21 22 group consisting of spacer pairs R and R , R and R , and R and R is used at the same time; Q is selected from the group consisting of N(R )SO2N(R )(R ),

N(R )C(O)OR , N(R )C(O)SR , N(R )C(S)OR and N(R )C(S)SR

23 24 26 with the proviso that no more than one of R , R , and R is hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the group consisting

23 24 26 of R , R , and R are bonded to the same atom;

Q is selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23_y 24 trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),

25 5 23 24 23 24

C(NR )SR , C(O)NR R , and C(O)NR R with the provisos that no

23 24 26 more than one of R , R , and R is hydroxy, alkoxy, alkylamino, amino, or

23 24 26 dialkylamino when two of the group consisting of R , R , and R are b bonded to the same atom and that said Q group is bonded directly to a carbon atom;

R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;

23 24

R and R are taken together to form a linear spacer moiety having from 4 through 7 contiguous atoms connecting the points of bonding to form a heterocyclyl ring having 5 through 8 contiguous members;

Q is selected from the group consisting of a single covalent bond,

37 38 n

(CR R )_|,-(W )_az wherein az is an integer selected from 0 through 1 , b is an integer selected from 1 through 4, and W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

(R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R^M), SC(S)N(R¹⁴),

14 14 15 14 14 15

SC(O)N(R ), OC(S)N(R ), N(R )C(O)N(R ), (R )NC(O)N(R ),

N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴),

14 8 7 8 8 7 14 N(R )S(O)₂, P(O)(R ), N(R )P(O)(R ), P(O)(R )N(R ), N(R ),

14 14 1 15

ON(R ), (CH(R ))_C-W -(CH(R ))_d wherein c and d are integers

independently selected from 1 through 4, and W is selected from the group

consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

14 14 14 14 14

(R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ), (R )NC(O)O,

14 14 14 14 14 SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S, OC(S)N(R ),

(R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),

15 14 14 15 14 N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R^?), N(R¹⁴),

14 14 2 15

ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein e and h are integers

independently selected from 0 through 2 and W^{^}^ is selected from the group

4a 4b 4a„4b consisting of CR =CR , ethynylidene (G≡C; 1,2-ethynyl), and C=CR R

14 15 with the provisos that R and R are selected from other than halo and cyano

37 38 14 14 when directly bonded to N and that (CR R )_b, (CH(R ))_C, (CH(R ))_e and are bonded to E ; 0 b ss ss Y is Q -Q wherein Q is selected from the group consisting of

37 38 14

(CR R )f wherein f is an integer selected from 1 through 6, (CH(R ))_c- 1 15

W -(CH(R ))^ wherein c and d are integers independently selected from 1

1 . 1 through 4, and W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,

14 14 14 14 14

C(O)N(R ),(R )NC(O), C(S)N(R ),(R )NC(S), OC(O)N(R ),

14 14 14 14 14 (R )NC(O)O, SC(S)N(R ),(R )NC(S)S, SC(O)N(R ),(R )NC(O)S,

14 14 15 14 14 15

OC(S)N(R ),(R )NC(S)O,N(R )C(O)N(R ),(R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ),(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 8 7 8 8 7 14

N(R )S(O)₂,P(O)(R ),N(R)P(O)(R ),P(O)(R )N(R ),N(R ),

14 14 2 15

ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein e and h are integers

independently selected from 0 through 2 and W^ is selected from the group

4a 4b 4a 4b consisting of CR =CR , ethynylidene (C≡C; 1,2-ethynyl), and C=CR R

14 15 with the provisos that R and R are selected from other than halo and cyano

37 38 15 when directly bonded to N and that (CR R )f, (CH(R ))_c , and

(CH(R¹⁵))_e are bonded to E°

38. Ϊ is Q -Q , wherein Q is (CH(R ))_r-W , r is an integer selected

3 from 1 through 3, and W is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3- morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4- moφholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 13-piperazinyl, 1,4-piperazinyl, 23-piperazinyl, 2,Spiperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3- pyπolidinyl, 2,3-pyπolidinyl, 2,4-pyπolidinyl, 2,5-ρyπolidinyl, 3,4-pyπolidinyl, 2H-2,3-ρyranyl, 2H-2,4-ρyranyl, 2H-2,5-ρyranyl, 4H-2,3-ρyranyl, 4H-2,4- pyranyl, 4H-2,5-ρyranyl, 2H-ρyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl, 4H- pyran-4-one-2,3-yl, 2,3-tetiahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 23-tetrahydropyranyl, 2,4- tetrahy dropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the proviso that (CH(R ))_r

is bonded to E and Q is bonded to lowest numbered substituent position of

each W ;

Y is Q -Q , wherein Q is (CH(R ))_r-W , r is an integer

4 selected from 1 through 3, and W is selected from the group consisting of 1,2- cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 23- orpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6- morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3-5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 1,3-pyπolidinyl, 2,3-pyπolidinyl, 2,4-pyπolidinyl, 2,5-pyπolidinyl, 3,4- pyπolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-23-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4_r5- yl, 4H-ρyran-4~one-23-yl, 23-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahy dropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the provisos that (CH(R ))_r

is bonded to is bonded to highest number substituent position of

4 each W ;

Y° is Q^b-Q^ssss, wherein Q^SSSS is (CH(R³⁸))_r- W⁵, r is an integer

selected from 1 through 3, and W^*^ is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, l,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothioρhenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyI, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3 ^-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naρhthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naρhthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinoUnyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W and that (CH(R ))_r is bonded to E°;

,i) . ~b „ssssr , . ~ssssr . _{( τ τ}, 8 6 . .

Y is Q -Q , wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 3, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3^-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2, benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzofhiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3 ,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1^- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each

W⁶ and that (CH(R³⁸))_r is bonded to E°.

3. The compound as recited in Claim 1 or a pharmaceutically acceptable salt thereof, wherein;

B is formula (V):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 2 1 1 2 1 2 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K 1 2 1 2 1 must be a covalent bond when two of D , D , J , J an K are O and S, and

1 2 1 2 1 no more than four of D , D , J , J and K are N;

32 33 34 35 36 b

R , R , R , R , and R are independently selected to be Q ;

R⁹ R¹⁰ R¹ R¹² R¹³, R¹⁶ R¹⁷, R¹⁸ R¹⁹ R³², R³³, R³⁴, R³⁵ and

R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, arylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, and diaralkoxyphosphonoalkyl;

B is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R3₂, R33, R34, R35, and R^g,

B is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or Rχ3, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ_> a ring carbon or nitrogen atom adjacent to the R₁ position and two atoms

from the point of attachment may be substituted with R_j2, a ring carbon or

nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_{j j} , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j2 position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34;

A is selected from the group consisting of single covalent bond, (W⁷)_rr-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W⁷)_rr wherein π is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O,

C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), and N(R⁷);

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

1 /1 1 ^ Ή ^

R , R , R , and R are independently selected from the group consisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl;

Ψ is selected from the group consisting of NR , O, C(O), C(S), S,

39 40 S(O), S(O)₂, and CR R ;

R is selected from the group consisting of hydrido, alkyl, and alkoxy;

39 40

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy, and haloalkoxyalkyl; X and R are independently selected from the group consisting of Z -

Q, hydrido, alkyl, alkenyl, and halo;

0 0

X and R are independently selected from the group consisting of amidino, guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono; Z is selected from the group consisting of covalent single bond,

41 42 41 (CR R )„ wherein q is an integer selected from 1 through 2, (CH(R ))_g- o 42

W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 2 and W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹),

(R⁴¹)NC(S), OC(O)N(R⁴¹), (R⁴¹)NC(O)O, SC(S)N(R⁴¹), (R⁴¹)NC(S)S,

SC(O)N(R⁴¹), (R⁴¹)NC(O)S, OC(S)N(R⁴¹), (R⁴¹)NC(S)O,

42 41 41 42 42 41 N(R )C(O)N(R ), (R )NC(O)N(R ), N(R )C(S)N(R ),

41 42 41 41 41

(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ), N(R )S(O)₂, N(R ),

ON(R⁴¹), and (CH(R⁴¹))_e-W²-(CH(R⁴²))_h wherein e and h are integers

independently selected from 0 through 2 and W^ is selected from the group

41 42 41 42 consisting of CR =CR , CR R =C; vinylidene), and ethynylidene (C≡C;

41 42

1 ,2-ethynyϊ), with the provisos that R and R are selected from other than halo and cyano when directly bonded to N and Z is directly bonded to the quinone ring;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl, and heteroaralkyl; Q is formula (II):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 2 1 1 2 1 1 no more than one of D , D , J , J and K is S, one of D , D , J , and K

1 2 1 2 1 must be a covalent bond when two of D , D , J , J and K are O and S, and

1 2 1 2 1 9 no more than four of D , D , J , J and K are N, with the proviso that R ,

10 11 12 13

R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

Q is selected from the group consisting of alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, saturated heterocyclyl, alkyl, partially saturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl;

4a„ 4b K is (CR R )_n wherein n is the integer 1;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, hydroxyalkyl, alkyl, alkoxyalkyl, and haloalkyl; E is E , when K is (CR R )_n, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R^?)NC(S), OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R^?)NC(S)S, SC(O)N(R⁷), (R^?)NC(O)S,

OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R^?), (R⁷)NC(O)N(R⁸),

N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂,

S(O)₂N(R⁷)C(O), C(O)N(R⁷)S(O)₂, N(R⁷), ON(R⁷), CR^4a=CR^4b,

4a 4b ethynylidene (C≡C; 1,2-ethynyl), and C=CR R ;

14 K is (CH(R )) -T wherein j is selected from a integer from 0 through

1 and T is selected from the group consisting of single covalent bond, O, S, and

7 14

N(R ) with the proviso that (CH(R )); is bonded to the quinone ring;

_^o . 2 ₁ „ . ,„„,,_, 14 , _^ , . Z . ,

E is E , when K is (CH(R ))]-T, wherein E is selected from the group consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O, C(O)S,

C(S)S, C(O)N(R⁷), (R^?)NC(O), C(S)N(R^?), (R^?)NC(S), (R⁷)NC(O)O,

(R⁷)NC(S)S, (R^?)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R^?),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R^?), (R⁷)NC(S)N(R⁸), S(O), S(O)₂,

S(O)₂N(R⁷), N(R^?)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, and N(R^?);

K is G-(CH(R ))_j- wherein k is the integer 1 and G is selected from

7 the group consisting of O, S, and N(R );

E is E , when K is G-(CH(R ))_},, wherein E is selected from the group consisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R^?)NC(S),

OC(O)N(R^?), (R^?)NC(O)O, SC(S)N(R^?), (R⁷)NC(S)S, SC(O)N(R^?),

(R⁷)NC(O)S, OC(S)N(R^?), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),

(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, rη rη rη rη ll_*

S(O)₂N(R ), N(R )S(O)₂, N(R ), ON(R ), CR ^&=CR , ethynylidene (C≡C;

4a 4b 1,2-ethynyl), and C=CR R ;

Y° is formula (IV):

JZ fZ £ rf-T wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one is a covalent bond, K is independently selected from the group

+ 5 6 5 6 consisting of C and N , no more than one of D , D , J , and J is O, no more

than one of D , D , J , and J is S, one of D , D , J , and J must be a 6 5 f covalent bond when two of D , D , J , and J are O and S, no more than three

of D , D , J , and J are N when K is N , and no more than four of D , D ,

5 /-ϊ 0 Λ f Λ H Λ R

J , and J are N when K is carbon with the provisos that R , R , R , and

19 R are each independently selected to maintain the tetiavalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, 20 ammoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R is hydroxy, alkoxy, alkylamino, amino, or dialkylamino and that

20 21 22

R , R , and R must be other than be hydroxy, alkoxy, alkylamino, ammo,

2 + and dialkylamino when K is N ;

Q is selected from the group consisting of N(R )SO₂N(R )(R ),

N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵

23 24 26 with the proviso that no more than one of R , R , and R is hydroxy, alkoxy, alkylamino, amino, or dialkylamino when two of the group consisting

23 24 26 of R , R , and R are bonded to the same atom;

Q is selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23 24 trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

26 26 25 23 24 26 26 23 24

N(R )N(R )C(NR )N(R )(R ), N(R )N(R )SO₂N(R )(R ),

25 5 23 24 23 24 C(NR )SR , C(O)NR R , and C(O)NR R with the provisos that no

23 24 26 more than one of R , R , and R is hydroxy, alkoxy, alkylamino, amino, or

dialkylamino when two of the group consisting of R , R , and R are

bonded to the same atom and that said Q group is bonded directly to a carbon atom;

23 24 25 26 R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl; Q is selected from the group consisting of a single covalent bond,

(CR R )iy(W )_az wherein az is an integer selected from 0 through 1, b is an integer selected from 1 through 2, and W is selected from the group consisting ofO, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),

14 14 14 14 14 (R )NC(O), C(S)N(R ),(R )NC(S), OC(O)N(R ), SC(S)N(R ),

14 14 15 14 14 15 SC(O)N(R ),OC(S)N(R ),N(R )C(O)N(R ),(R )NC(O)N(R ),

15 14 14 15 14

N(R )C(S)N(R ),(R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 14 14 14 1 15

N(R )S(O)₂, N(R ), ON(R ), (CH(R ))_C-W -(CH(R ))_d wherein c

and d are integers independently selected from 1 through 2, and W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,

14 14 14 14 14

C(O)N(R ), (R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ),

(R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S,

14 14 15 14 14 15

OC(S)N(R ), (R )NC(S)O, N(R )C(O)N(R ), (R )NC(O)N(R ),

15 14 14 15 14 N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 14 14 14 2 15 N(R )S(O)₂, N(R ), ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein

e and h are integers independently selected from 0 through 2 and W"^ is

4a 4b selected from the group consisting of CR =CR , ethynylidene {C≡C; 1,2-

4a_τ,4b 14 15 ethynyl), and C=CR with the provisos that R and R are selected from other than halo and cyano when directly bonded to N and that

37 38 14 14 o (CR R )_b, (CH(R ))_c, and (CH(R ))_e are bonded to E ; π b ss ss

Y is Q -Q wherein Q is selected from the group consisting of

37 38 14

(CR R )f wherein f is an integer selected from 1 through 4, (CH(R ))_c- W -(CH(R ))_d wherein c and d are integers independently selected from 1

through 2, and W is selected from the group consisting of W is selected from the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,

14 14 14 14 14

C(O)N(R ), (R )NC(O), C(S)N(R ), (R )NC(S), OC(O)N(R ),

14 14 14 14 14 (R )NC(O)O, SC(S)N(R ), (R )NC(S)S, SC(O)N(R ), (R )NC(O)S,

OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),

15 14 14 15 14

N(R )C(S)N(R ), (R )NC(S)N(R ), S(O), S(O)₂, S(O)₂N(R ),

14 14 14 14 2 15

N(R )S(O)₂, N(R ), ON(R ), and (CH(R ))_e-W -(CH(R ))_h wherein

e and h are integers independently selected from 0 through 2 and W^ is

4a 4b selected from the group consisting of CR =CR , ethynylidene (Gs 1,2-

4a 4b 14 15 ethynyl), and C=CR R with the provisos that R and R are selected

37 38 from other than halo when directly bonded to N and that (CR R )f ,

(CH(R ))_c, and (CH(R ))_e are bonded to E°;

_Ω h sss sss o j i is Q -Q wherein Q is (CH(R ))_r-W , r is an integer selected

from 1 through 2, and W is selected from the group consisting of 1,1- cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 13-cyclopentyl, 2,3- morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4- morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piρerazinyl, 23-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 23-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piρeridinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3- pyrrolidinyl, 23-pyrrolidinyl, 2,4-ρyπolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-23-ρyranyl, 2H-2,4-ρyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4- pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-ρyran-2-one-4,5-yl, 4H- pyran-4-one-23-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahy dropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the proviso that (CH(R ))_r

is bonded to E and Q is bonded to lowest numbered substituent position of

each W ;

Ϊ is Q -Q wherein Q is (CH(R ))_r-W , r is an integer

4 selected from 1 through 2, and W is selected from the group consisting of 1,2- cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3- cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6- morpholinyl, 3,4-morpholinyl, 3,5-moφholinyl, 1,2-piperazinyl, 13-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyπolidinyl, 13-pyrrolidinyl, 23-pyrrolidinyl, 2,4-ρyrrolidinyl, 2,5-ρyrrolidinyl, 3,4- pyπolidinyl, 2H-2,3-ρyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5- yl, 4H-pyran-4-one-2,3-yl, 23-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5- tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4- tetrahy dropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-

38 tetrahydropyranyl, and 3, 5-tetrahy dropyranyl with the provisos that (CH(R ))_r

is bonded to E and Q is bonded to highest number substituent position of

4 each W ;

Y is Q -Q wherein Q is (CH(R ))_r- W , r is an integer

selected from 1 through 2, and W~^{^} is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3 ,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naρhthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W and that (CH(R³⁸))_r is bonded to E°;

38 Y° is Q^b-Q^ssssr wherein Q^SSSSr is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,Sindolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1^- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naρhthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naρhthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinohnyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3,Sisoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl , 4,5-cinnolinyl, 4,6-cinnolinyl , 4,7-cinnolinyl , and 4,8-cinnolinyl with the proviso that Q is bonded to highest number substituent position of each dZ Q

W and that (CH(R ))_r is bonded to E°.

4. The compound as recited in Claim 3 or a pharmaceutically acceptable salt thereof, wherein;

B is formula (V):

1 2 1 2 1 wherein D , D , J , J and K are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 2 1 1 2 1 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K

must be a covale bond when two of D¹, D², Λ ² and K¹ are O and S, and „32 33 34 35 _J „36 . , _n , , _Λ , ^b R , R , R , R , and R are independently selected to be Q ; n9 _π10 _nll _n12 _n13 32 33 34 5 36

R , R , R , R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, alkenyloxy, alkenyloxyalky, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido, carboalkoxyaikyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, and cyano; B is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl,

C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆; B is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or Rγ^, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ, a ring carbon or nitrogen atom adjacent to the R₁ position and two atoms

from the point of attachment may be substituted with R_j , a ring carbon or nitrogen atom three atoms from the point of attachment and adjacent to the RJQ

position may be substituted with R_j γ , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the Rγ position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R _j and R33 positions may be

substituted with R34;

A is selected from the group consisting of single covalent bond,

1 1 ^ 1 *ζ 1

(W )_rr-(CH(R ))_pa and (CH(R ))_pa-(W )_n wherein π is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, C(O), C(S), C(O)S, C(S)O,

C(O)N(R⁷), C(S)N(R^?), (R⁷)NC(O), (R^?)NC(S), S(O), S(O)₂, S(O)₂N(R⁷),

(R⁷)NS(O)₂, C(NR^?)N(R⁷), (R⁷)NC(NR⁷), and N(R⁷) with the proviso that no more than one of the group consisting of π and pa is 0 at the same time;

7 8

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; Ψ is NH;

X is hydrido;

7 0 R is selected from the group consisting of Z -Q, hydrido, alkyl, alkenyl, and halo; ZZ iiss aa CcOoTvalent single bond; Q is formula (II) consisting of C, N, O, S and a covalent bond with the provisos that no more

1 2 1 2 1 . than one is a covalent bond, no more than one of D , D , J , J and K is O,

1 2 1 ,2 1 1 2 1 1 no more than one of D , D , J , J and K is S, one of D , D , J , J and K

1 2 1 2 1 must be a covalent bond when two of D ,, DD ,, JJ ,, T J aanndd KK are O and S, and

1 2 1 2 1 9 no more than four of D , D , J , J and K are N, with the proviso that R ,

R , R , R , and R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

4a 4b K is CR R ;

4a 4b

R and R are independently selected from the group consisting of halo, hydrido, hydroxy, alkyl, and haloalkyl; o 1 4a 4b 1

E is E , when K is CR R , wherein E is selected from the group consisting of a covalent single bond, (O)N(H), (H)NC(O), C(S)N(H),

(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

14 K is (CH(R )):-T wherein j is selected from an integer from 0 through

1 and T is selected from the group consisting of single covalent bond and

7 14

N(R ) with the proviso that (CH(R )) is bonded to the quinone ring; 14 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

E is E , when K is (CH(R )) -T, wherein E is selected from the

group consisting of C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; Y° is formula (IV):

r- C (Z wherein D , D , J , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one is a covalent bond, K is independently selected from the group

consisting of C and N , no more than one of D , D , J , and J is O, no more

5 6 5 6 5 6 5 6 than one of D , D , J , and J is S, one of D , D , J , and J must be a

5 6 5 6 covalent bond when two of D , D , J , and J are O and S, no more than three

C f -G ( -C έZ of D , D , J , and J are N when K is N , and no more than four of D , D , fi 0 16 17 18 J , and J are N when K is carbon with the provisos that R , R , R , and

19 R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen; „ 16 „17 „18 _{J T1}19 . , , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, carboalkoxyaikyl, and cyano; b 20 21 + 20 21 22

Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,

20 aminoalkyl, and hydroxyalkyl with the provisos that no more than one of R ,

21 22

R , and R is hydroxy, alkoxy, alkylamino, amino, or dialkylamino and that

20 21 22

R , R , and R must be other than be hydroxy, alkoxy, alkylamino, amino,

2 + or dialkylamino when K is N ; b 26 23 24 Q is N(R )SO₂N(R )(R ) with the proviso that no more than one

23 24 26 of R , R , and R is hydroxy, alkoxy, alkylamino, ammo, or dialkylamino

23 24 26 when two of the group consisting of R , R , and R are bonded to the same atom;

23 24 25 26

R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl;

Q is selected from the group consisting of dialkylsulfonium,

25 23 24 26 25 23 24 trialkylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴),

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), 26 26 25 23 24 26 26 23 24

N(R )N(R )C(NR )N(R )(R ), N(R )N(R )SO₂N(R )(R ),

23 24 23 24

C(O)NR R , and C(O)NR R with the provisos that no more than one of

2 _n24 _{1 n}26 . , , „

R , R , and R is hydroxy, alkoxy, alkylamino, amino, or dialkylamino when

23 24 26 two of the group consisting of R , R , and R are bonded to the same atom and

that said Q group is bonded directly to a carbon atom; g

Q is selected from the group consisting of a single covalent bond and

(CR R )χ_j-(W )_az wherein az is an integer selected from 0 through 1, b is an integer selected from 1 through 2, and W is selected from the group consisting

14 14 14 of O, S, C(O), S(O)₂, N(R ), and ON(R ) with the proviso that R is

37 38 selected from other than halo when directly bonded to N and that (CR R ) , is bonded to E ;

37 38

R and R are independently selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

Y is Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and W^*^ is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzoιhiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naρhthyl, 1,5-naρhthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, l,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso that Q is bonded to lowest number substituent position of each

W⁵ and that (CH(R³⁸))_r is bonded to E°;

Y is Q -Q wherein Q is (CH(R ))_r-W , r is an integer

selected from 1 through 2, and W is selected from the group consisting of 1,4- indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5- indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4- benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4- benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl, 2,4- benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7- benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6- benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7- indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5- isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7- isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7- indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7- benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7- benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naρhthyl, 1,8- naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4- quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5- quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinoUnyl, 1,4-isoquinolinyl, 1,5- isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4- isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8- isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8- isoquinolinyl, 3,4-cinnoUnyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8- cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with

0) . the proviso that Q is bonded to highest number substituent position of each

W and that (CH(R ))_r is bonded to E°.

5. The compound as recited in Claim 4 having the Formula I-S:

or a pharmaceutically acceptable salt thereof, wherein; B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-ρyπolyl, 2-imidazolyl, 4-imidazolyl, 3-ρyrazolyl, 4-pyrazolyl, l,2,4-triazol-3-yl, l,2,4-triazol-5-yl, l,2,4-oxadiazol-3-yl, 1,2,4- oxadiazol-5-yl, 13,4-oxadiazol-3-yl, 1,3,4-oxadiazol- yl, 3-isothiazolyl, 5- isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3- pyridazinyl, 4-pyridazinyl, 13,5-triazin-2-yl, l,2,4-triazin-3-yl, l,2,4-triazin-5-yl, l,2,4-triazin-6-yl, and l,2,3-triazin-4-yl, wherein a carbon adjacent to the carbon

32 at the point of attachment may be substituted by R , the other carbon adjacent

36 to the carbon at the point of attachment may be substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment may

be substituted by R , a carbon adjacent to R and two atoms from the carbon

35 at the point of attachment may be substituted by R , and any carbon adjacent

33 35 34 to both R and R may be substituted by R ; 32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,33- pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, cyano, and Q ; B is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, isobutyl, 2- methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3- pentynyl, 2-pentyl, l-methyl-2-butenyl, l-methyl-3-butenyl, l-methyl-2- butynyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2- methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3- methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2- hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3- pentenyl, l-methyl-4-pentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3- hexyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, 1 -propyl -2-ρroρenyl, l-ethyl-2- butynyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heρtenyl, 5-heptenyl, 6-heptenyl, 2- heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heρtyl, l-methyl-2-hexenyl, 1- methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-5-hexenyl, l-methyl-2- hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-4-pentenyl, l-butyl-2-proρenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 1-octyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl,

7-octenyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl, 1- methyl-2-heptenyl, l-methyl-3-heptenyl, l-methyl-4-heptenyl, l-methyl-5- heptenyl, l-methyl-6-heptenyl, l-methyl-2-heptynyl, l-methyl-3-heptynyl, 1- methyl-4-heptenyl, 1-methyl-Sheρtenyl, l-methyl-6-heptenyl, l-methyl-2- heptenyl, l-methyl-3-heρtynyl, l-methyl-4-heptynyl, l-methyl-5-heρtynyl, 3- octyl, l-ethyl-2-hexenyl, l-ethyl-3-hexenyl, l-ethyl-4-hexenyl, l-ethyl-2- hexynyl, l-ethyl-3-hexynyl, l-ethyl-4-hexynyl, l-ethyl-5-hexenyl, l-pentyl-2- propenyl, 4-octyl, l-propyl-2-ρentenyl, l-ρropyl-3-ρentenyl, l-ρroρyl-4- pentenyl, l-butyl-2-butenyl, l-propyl-2-pentynyl, l-propyl-3-pentynyl, 1-butyl- 2-butynyl, l-butyl-3-butenyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5,5- trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,33- trifluoropropyl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group consisting of R3₂, R33, R34, R3 , and ^f,;

B is selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, cyclopentyl, cyclopent-2-enyl, cyclopent-3-enyl, cyclohexyl, 4- methylcyclohexyl, 4-chloro-3-ethylphenoxycyclohexyl, 3- trifluoromethoxyphenoxycyclohexyl, 3-trifluoromethylcyclohexyl, 4- trifluoromethylcyclohexyl, 3,5-bis-trifluoromethylcyclohexyl, adamantyl, 3- trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl, norbornenyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl, cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl, cyclooct-4-enyl, 2-morpholinyl, 3- morpholinyl, 4-moφholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2- piperidinyl, 3-ρiperidinyl, 4-piperidinyl, 1 -pyπolidinyl, 2-ρyπolidinyl, 3- pyπolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-4-pyranyl, 4H-2- pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 2H-pyran-2-one-3-yl, 2H-ρyran-2-one- 4-yl, 2H-ρyran-2-one-5-yl, 4H-ρyran-4-one-2-yl, 4H-ρyran-4-one-3-yl, 2- tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3- tetrahy dropyranyl, 4-tetrahydropyranyl, 2-tetrahy drothienyl, and 3- tetrahydrothienyl, wherein each ring carbon may be optionally substituted with

R33, a ring carbon and nitrogen atoms adjacent to the carbon atom at the point

of attachment may be optionally substituted with R9 or Rχ3, a ring carbon or

nitrogen atom adjacent to the R9 position and two atoms from the point of

attachment may be substituted with RJQ, and a ring carbon or nitrogen atom adjacent to the R^ position and two atoms from the point of attachment may

be substituted with Rχ₂;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, dimethylsulfonium, methylethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, butoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- dimethylamino, N-methylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl, N,N- dimethylamidosulfonyl, acetyl, propanoyl, butanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxy ethyl, 2,2,2- tiifluoro- 1 -hydroxyethyl, 2,2,2-trifluoro- 1 -trifluoromethyl- 1 -hydroxyethyl, carboxymethyl, 2-carboxy ethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano; A is selected from the group consisting of single covalent bond, O,

C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), C(O)CCH₃,

C(O)CCF₃, CH₂C(O), (O)CCH₂, CH₂CH₂, CH₂CH₂CH₂, CH₃CCH₂,

CF₃CCH₂, CH₃CC(O)CH₂, CF₃CC(O)CH₂, CH₂C(O)CCH₃,

CH₂C(O)CCF₃, CH₂CH₂C(O), and CH₂(O)CCH₂;

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-ρyrrolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-ρyrazolyl, 4-ρyrazolyl, l,2,4-triazol-3-yl, l,2,4-triazol-5-yl, l,2,4-oxadiazol-3-yl, 1,2,4- oxadiazol-5-yl, 13,4-oxadiazol-3-yl, l,3,4-oxadiazol-5-yl, 3-isothiazolyl, 5- isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3- pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3- pyridazinyl, 4-pyridazinyl, l,3,Striazin-2-yl, l,2,4-triazin-3-yl, 1,2,4-triazin- yl, l,2,4-triazin-6-yl, and l,23-triazin-4-yl, wherein a carbon adjacent to the carbon

9 at the point of attachment may be substituted by R , the other carbon adjacent

13 to the carbon at the point of attachment may be substituted by R , a carbon 9 adjacent to R and two atoms from the carbon at the point of attachment may be

10 13 substituted by R , a carbon adjacent to R and two atoms from the carbon at

12 the point of attachment may be substituted by R , and any carbon adjacent to , 10 12 , . 11 both R and R may be substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido; o 1 4a 4b 1

E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K is selected from the group consisting of N(H) and CH₂N(H); o 2 2

E is E , when K is N(H) and CH₂N(H), wherein E is selected from

the group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; ϊ is selected from the group of formulas consisting of:

„ 16 17 _^18 19 . , ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333- pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1-hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, and cyano; Q is selected, when bonded to a carbon, from the group consisting of

20 21 ₊ 20 21 22 NR R , NR R R , dimethylsulfonium, methylethylsulfonium,

25 23 24 diethylsulfonium, trimethylphosphonium, C(NR )NR R ,

N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),

23 24 23 24 C(O)NR R , and C(O)NR R with the provisos that no more than one of

20 21 22

R , R , and R is hydroxy, methoxy, ethoxy, N-methylamino, N,N- dimethylamino, N,N,N-trimethylamino, or amino and that no more than one of

23 24 26

R , R , andR is hydroxy, methoxy, ethoxy, N-methylamino, N,N- dimethylamino, N,N,N-trimethylamino, or amino when two of the group

. . ._^23 24 26 , , , , . , _Λb consisting of R , R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, hydroxy, methoxy, ethoxy, isopropoxy, propoxy, 2-aminoethyl, 2-(N-methylamino)ethyl, 2- (N,N-dimeιhylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl, N-(2- hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2- aminoethyl)amino, N-methylamino, N-ethylamino, N,N-dimethylamino, N,N- diethylamino, and N,N,N-trimethylamino;

Q is selected, when bonded to a nitrogen, from the group consisting of oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N- dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino, N-methoxyamino, N- methylamino, N,N-dimethylamino, and N,N,N-trimethylamino; Q is selected from the group consisting of a single covalent bond, CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S,

CF₃C(H)S, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the s 0 proviso that Q is bonded to E through a carbon atom.

6. The compound as recited in Claim 1 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment may be substituted by

32 R , the other carbon adjacent to the carbon at the point of attachment may be

36 32 substituted by R , a carbon adjacent to R and two atoms from the carbon at

33 36 the point of attachment may be substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment may be substituted by

35 33 35 34

R , and any carbon adjacent to both R and R may be substituted by R ;

32 33 34 35 36 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy, carboxamido, cyano, and

Q^b;

B is selected from the group consisting of C3-C8 alkyl, C3-C8 alkenyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member of group B may be optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more of the group consisting of

^R32> ^R33' ^R34> ^R35' ^{md R}36'

B is selected from the group consisting of C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partially saturated heterocyclyl, wherein each ring carbon may be optionally substituted with R33, a ring carbon other than the ring carbon at the point of attachment of B to A may be optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or RJ3, a ring carbon or nitrogen atom adjacent to the R9 position and two atoms from the point of attachment may be substituted with

RJQ, a ring carbon or nitrogen atom adjacent to the R_j3 position and two atoms

from the point of attachment may be substituted with R_j2, a ring carbon or

nitiogen atom three atoms from the point of attachment and adjacent to the R JQ

position may be substituted with R_{j j} , a ring carbon or nitrogen atom three

atoms from the point of attachment and adjacent to the R_j position may be

substituted with R33, and a ring carbon or nitrogen atom four atoms from the

point of attachment and adjacent to the R_{j j} and R33 positions may be

substituted with R34;

9 10 11 12 13 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy, carboxamido, and cyano; A is selected from the group consisting of single covalent bond,

(W⁷)_rτ-(CH(R¹⁵))_pa and (CH(R¹⁵))_pa-(W^?)_rr wherein rr is an integer

7 selected from 0 through 1, pa is an integer selected from 0 through 6, and W is selected from the group consisting of O, S, and C(O) with the proviso that no more than one of the group consisting of rr and pa is the integer 0 at the same time; R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; Ψ is NH;

X^ is hydrido; R is Q, wherein Q is selected from the group consisting of aryl and heteroaryl wherein a carbon adjacent to the carbon at the point of attachment

9 may be substituted by R , the other carbon adjacent to the carbon at the point of

13 9 attachment may be substituted by R , a carbon adjacent to R and two atoms

from the carbon at the point of attachment may be substituted by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment may

be substituted by R , and any carbon adjacent to both R and R may be

11 substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of halo and hydrido; o 1 4a 4b 1 E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

14 K is (CH(R )):-T wherein j is selected from an integer from 0 through

1 and T is selected from the group consisting of single covalent bond and

7 14 N(R ) with the proviso that (CH(R ))j is bonded to the quinone ring;

7 R is selected from the group consisting of hydrido, hydroxy, alkyl, and alkoxyalkyl;

14 . .

R is selected from the group consisting of hydrido and halo; o 2 14 2

E is E , when K is (CH(R )):-T, wherein E is selected from the

group consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,

S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; Y° is formula (IV):

_^5 5 . β wherein DD ,, DD ,, JJ , and J are independently selected from the group consisting of C, N, O, S and a covalent bond with the provisos that no more

2 than one is a covalent bond, K is independently selected from the group

. . „ , „+ , 5 6 _τ5 6 _Λ consisting of C and N , no more than one of D , D , J , and J is O, no more

5 6 5 6 5 6 5 6 than one of D , D , J , and J is S, one of D , D , J , and J must be a 6 f covalent bond when two of D , D , J , and j are O and S, no more than three

of D , D , J , and J are N when K is N , and no more than four of D , D ,

5 6 0 16 17 I S

J , and J are N when K is carbon with the provisos that R , R , R , and

19 R are each independently selected to maintain the tetravalent nature of carbon, trivalent nature of nitrogen, the divalent nature of sulfur, and the divalent nature of oxygen;

16 17 18 1

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy, haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, carboalkoxyaikyl, and cyano; b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylamino

20 21 22 wherein R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, a— _yl, and h_yd_roχ_ya,_ky, «* .he provisos that _no _more than one of R²⁰,

21 22

R , and R is hydroxy, alkoxy, alkylamino, am o, or dialkylamino and that

20 21 22

R , R , and R must be other than be hydroxy, alkoxy, alkylamino, amino,

2 + or dialkylamino when K is N ;

Q is selected from the group consisting of dialkylsulf onium,

trialkylphosphonium,

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

26 26 23 24 23 24 23 24

N(R )N(R )SO₂N(R )(R ), C(O)NR R , and C(O)NR R with

23 24 26 the provisos that no more than one of R , R , andR is hydroxy, alkoxy,

23 alkylamino, ammo, or dialkylamino when two of the group consisting of R ,

24 26 b

R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

^*73 OΔ. 95 Of

R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino, aminoalkyl, and hydroxyalkyl; s Q is selected from the group consisting of a single covalent bond and

(CR R )χ_j-(W )_az wherein az is an integer selected from 0 through 1, b is the integer 1, and W is selected from the group consisting of O, S, and C(O) with the proviso that (CR R )tø is bonded to E ;

37 38

R and R are independently selected from the group consisting of hydrido, halo, alkyl, and haloalkyl.

7. The compound as recited in Claim 6 having the Formula I-MPS:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-ρyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

32 the point of attachment may be substituted by R , the other carbon adjacent to

36 the carbon at the point of attachment may be substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment may

33 36 be substituted by R , a carbon adjacent to R and two atoms from the carbon

35 at the point of attachment may be substituted by R , and any carbon adjacent

33 35 34 to both R and R may be substituted by R ;

32 33 34 35 36 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3- pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l -hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1 -hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, cyano, and Q ;

B is selected from the group consisting of 1-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl, 2-methylpropenyl, 1- pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentyl, l-methyl-2-butenyl, 1- methyl-3-butenyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2- butenyl, 2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3- butenyl, 2,2-difluoropropyl, 2-trifluoromethyl-3,33-trifluoropropyl, 1,1,1,2,2,2- hexafluoropropyl, 3,3,3-trifluoroprop-l-yl, and 3,3 -trifluoroprop-2-yl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group consisting of R₃₂, R33, R34, R35, and R_3fi;

B is selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, wherein each ring carbon may be optionally substituted with R33, a ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R^, a ring carbon or

nitrogen atom adjacent to the R9 position and two atoms from the point of

attachment may be substituted with RJQ, and a ring carbon or nitrogen atom

adjacent to the R_j position and two atoms from the point of attachment may

be substituted with R_j2; 9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, dimethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1- hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, 2,2,2-trifluoro-l- trifluoromethyl-1 -hydroxyethyl, carboxymethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N- dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O,

C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), CC(O)CCH₃,

C(O)CCF₃, CH₂C(O), and (O)CCH₂;

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,

2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

9 the point of attachment may be substituted by R , the other carbon adjacent to

13 the carbon at the point of attachment may be substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment may be

substituted by R , a carbon adjacent to R and two atoms from the carbon at

the point of attache _ma_y he suhstituted h_y R¹², and a»_y ca hon adjacent to

10 12 11 both R and R may be substituted by R ;

4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido; E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K is selected from the group consisting of N(H) and CH₂N(H); o 2 E is E , when K is selected from the group consisting of N(H) and

2 CH₂N(H), wherein E is selected from the group consisting of C(O)N(H),

(H)NC(O), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; ϊ is selected from the group of formulas consisting of:

_^ 16 _ 17 18 , ,-.19 . , , , , , , , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methoxy, ethoxy, isopropoxy, methylthio, ethylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2- tetrafluoroethoxy, fluoro, chloro, bromo, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, methoxy carbonyl, ethoxy carbonyl, and cyano;

Q is selected, when bonded to a carbon, from the group consisting of

20 21 ₊ 20 21 22 NR R , NR R R , dimethylsulfonium, methylethylsulfonium,

25 23 24 diethylsulfonium, trimethylphosphonium, C(NR )NR R , f £Z _'ζ OA Of. *Z * A

N(R )C(NR )N(R )(R ), C(O)N(R )C(NR )N(R )(R ),

N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴),

23 24 23 24

C(O)NR R , and C(O)NR R with the provisos that no more than one of 20 21 22

R , R , and R is hydroxy, methoxy, ethoxy, N-methylammo, N,N- dimethylamino, N,N,N-trimethylamino, or amino and that no more than one of

23 24 26

R , R , and R is hydroxy, methoxy, ethoxy, N-methylamino, N,N- dimethylamino, N,N,N-trimethylamino, or amino when two of the group

23 24 26 b consisting of R , R , and R are bonded to the same atom and that said Q group is bonded directly to a carbon atom;

20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2- aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl, 2-(N,N,N- trimethylamino)ethyl, N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino, N,N-dimethylamino, and N,N,N-trimethylamino;

Q is selected, when bonded to a nitrogen, from the group consisting of oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N- dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl , N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino, hydroxylamino, N-methoxyamino, N- methylamino, N,N-dimeιhylamino, and N,N,N-trimethylamino; g

Q is selected from the group consisting of a single covalent bond, CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S, CF₃C(H)S , CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the s 0 proviso that Q is bonded to E through a carbon atom.

8. The compound as recited in Claim 7 having the Formula I-EMPS:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-ρyrrolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazoιyl, 3-pyrazolyl, 4-ρyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, and 4- pyridyl, wherein a carbon adjacent to the carbon at the point of attachment may

32 be substituted by R , the other carbon adjacent to the carbon at the point of

attachment may be substituted by R , a carbon adjacent to R and two atoms

33 from the carbon at the point of attachment may be substituted by R , a carbon

adjacent to R and two atoms from the carbon at the point of attachment may

35 33 35 be substituted by R , and any carbon adjacent to both R and R may be

34 substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methoxy, ethoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2- aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l- hydroxyethyl, 2,2,2-trifluoro-l-trifluoromethyl-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, cyano, and Q ; B is selected from the group consisting of propyl, isopropyl, butyl, sec- butyl, isobutyl, 1-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2- difluoropropyl, 2-trifluoromethyl-333-trifluoropropyl, 1,1,1,2,2,2- hexafluoropropyl, 3,3,3-trifIuoroprop-l-yl, and 3,33-trifluoroprop-2-yl, wherein each member of group B may be optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group consisting of R ₂, R33, R34, R35, and R^f,

B is selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, fhiaeιan-2-yl, thiaetan-3-yl, wherein each ring carbon may be optionally substituted with R33, a ring carbon and nitrogen atoms adjacent to the carbon atom at the point of attachment may be optionally substituted with R9 or R_j , a ring carbon or

nitrogen atom adjacent to the Rg position and two atoms from the point of

attachment may be substituted with R Q, and a ring carbon or nitrogen atom

adjacent to the R_j position and two atoms from the point of attachment may

be substituted with R_j2;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of amidino, guanidino, carboxy, methoxy, ethoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N- methylamino, dimethylamino, N-ethylamino, acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxymethyl, methoxy carbonyl, ethoxycarbonyl, amidocarbonyl, N- methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O, C(O), CH₂, CH₂C(O), and (O)CCH₂;

R is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-ρyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-ρyridyl, 3-pyridyl, 4- pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-ρyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-ρyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at

9 the point of attachment may be substituted by R , the other carbon adjacent to

13 the carbon at the point of attachment may be substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment may be

10 13 substituted by R , a carbon adjacent to R and two atoms from the carbon at

12 the point of attachment may be substituted by R , and any carbon adjacent to

10 12 11 both R and R may be substituted by R ; 4a 4b 4a 4b

K is CR R wherein R and R are independently selected from the group consisting of chloro, fluoro, and hydrido;

E is E , when K is CR R , wherein E is selected from the group

consisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),

N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K is selected from the group consisting of N(H) and CH N(H); o 2 E is E , when K is selected from the group consisting of N(H) and

2 CH2N(H), wherein E is selected from the group consisting of C(O)N(H),

(H)NC(O), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; Y is selected from the group of formulas consisting of:

16 17 18 1 Q R , R , R , and R are independently selected from the group consisting of hydrido, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, trifluoromethoxy, fluoro, chloro, bromo, acetyl, trifluoroacetyl, methoxycarbonyl, ethoxy carbonyl, and cyano; b 20 21 ₊ 20 21 22

Q is selected from the group consisting of NR R , NR R R , dimethylsulfonium, methylethylsulfonium, diethylsulfonium,

25 23 24 26 25 23 24 trimethylphosphonium, C(NR )NR R , N(R )C(NR )N(R )(R ),

C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),

N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with

20 21 22 the provisos that no more than one of R , R , andR is hydroxy, methoxy, ethoxy, N-methylamino, NJSf-dimethylamino, and N,N,N-trimethylamino, or amino and that no more than one of R , R , and R is hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino, or amino

23 24 26 when two of the group consisting of R , R , and R are bonded to the same atom;

20 21 22 23 24 25 26

R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, hydroxy, methoxy, ethoxy, 2- aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl, 2-(N,N,N- trimethylamino)ethyl , N-(2-hy droxy ethyl)amino, N,N-bis-(2-hy droxy ethyl)amino, N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino, N,N-dimethylamino, and N,N,N-trimethylamino; s Q is selected from the group consisting of a single covalent bond, CH₂,

CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂C(O),

CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with the proviso that Q^s is bonded to E through a carbon atom.

9. A composition for inhibiting thrombotic conditions in blood comprising a compound of any one of Claims 1 through 8 and a pharmaceutically acceptable carrier.

10. A method for inhibiting thrombotic conditions in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 9.

11. A method for inhibiting formation of blood platelet aggregates in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 9.

12. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 9.

13. A method for treating or preventing venuous thromboembolism and pulmonary embolism in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

14. A method for treating or preventing deep vein thrombosis in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

15. A method for treating or preventing cardiogenic thromboembolism in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

16. A method for treating or preventing thromboembolic stroke in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

17. A method for treating or preventing thrombosis associated with cancer and cancer chemotherapy in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

18. A method for treating or preventing unstable angina in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 9.

19. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of a compound of any one of Claims 1 through 8 with a therapeutically effective amount of fibrinogen receptor antagonist.

20. The use of a compound of any one of Claims 1 through 8, or a pharmaceutically acceptable salt thereof, in the manufacture of medicament for inhibiting thrombus formation, treating thrombus formation, or preventing thrombus formation in a mammal.

21. A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogen with a removable hydrogen or a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to A is optionally substituted by

32 R , a nitrogen with a removable hydrogen or a carbon at the other position

" 6 adjacent to the point of attachment is optionally substituted by R , a nitrogen

32 with a removable hydrogen or a carbon adjacent to R and two atoms from the

33 point of attachment is optionally substituted by R , a nitrogen with a

_removab,e h_yd_rogen or a carbon adjacent to R^M and two ato_ms tan the point

35 of attachment is optionally substituted by R , and a nitrogen with a removable

33 35 hydrogen or a carbon adjacent to both R and R is optionally substituted by

34

R

9 10 11 12 13 32 33 34 35 36

R , R , R , R , R , R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy, carboxamido, carboxamidoalkyl, and cyano;

32 33 34 35 36 b

R , R , R , R , and R are independently optionally Q ;

B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A

32 33 34 35 36 with one or more of the group consisting of R , R , R , R , and R ;

B is optionally a C3-C12 cycloalkyl or C4-C9 saturated heterocyclyl,

33 wherein each ring carbon is optionally substituted with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon

9 13 atom at the point of attachment are optionally substituted with R or R , a ring

9 carbon or nitrogen atom adjacent to the R position and two atoms from the

point of attachment is optionally substituted with R , a ring carbon or nitrogen

13 adjacent to the R position and two atoms from the point of attachment is

12 optionally substituted with R , a ring carbon or nitrogen three atoms from the

point of attachment and adjacent to the R position is optionally substituted

with R , a ring carbon or nitrogen three atoms from the point of attachment

12 33 and adjacent to the R position is optionally substituted with R , and a ring carbon or nitrogen four atoms from the point of attachment and adjacent to the

11 33 34

R and R positions is optionally substituted with R ;

A is selected from the group consisting of a bond,

1 1 * 1 * Ή

(W )_rr-(CH(R )) and (CH(R ))_pa-(W )_n wherein rr is 0 or 1 , pa is an

7 integer selected from 0 through 6, and W is selected from the group

7 7 7 consisting of O, S, C(O), (R )NC(O), (R )NC(S), and N(R ) with the proviso that no more than one of the group consisting of rr and pa is 0 at the same time;

7 R is selected from the group consisting of hydrido, hydroxy, and alkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl;

Ψ is NH or NOH;

X is selected from the group consisting of hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q; o 41 42

Z is selected from the group consisting of a bond, (CR R )_q

41 o wherein q is an integer selected from 1 through 3, and (CH(R ))_g-W -

42 (CH(R ))p wherein g and p are integers independently selected from 0 through 3 and W is selected from the group consisting of O, S, C(O), S(O),

41 41

N(R ), and ON(R );

Z° is optionally (CH(R⁴¹))_e-W²²-(CH(R⁴²))_h wherein e and h are

independently 0 or 1 and W^ is selected from the group consisting of

41 42 CR =CR , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 13-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morρholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-ρiρerazinyl, 13-piρerazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 13-piperidinyl, 2,3-piperidinyl, 2,4-ρiperidinyl, 2,6-piperidinyl, 3,4-ρiperidinyl, 1,2-pyπolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-ρyrrolidinyl, 3,4-pyπolidinyl, 23-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,

2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1,4-quinone ring and W^{^}^ is optionally substituted with one or more

substituents se ,lected from the group consi •sti •ng o .f _^ R⁹ , T R,¹⁰ , τ R,U , „ R12 , and _^ R13 ;

41 42

R and R are independently selected from the group consisting of amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogen with a removable hydrogen or a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is optionally substituted by

9

R , a nitrogen with a removable hydrogen or a carbon at the other position

13 adjacent to the point of attachment is optionally substituted by R , a nitrogen

9 with a removable hydrogen or a carbon adjacent to R and two atoms from the

point of attachment is optionally substituted by R , a nitrogen with a

13 removable hydrogen or a carbon adjacent to R and two atoms from the point

12 of attachment is optionally substituted by R , and a nitrogen with a removable

10 12 hydrogen or a carbon adjacent to both R and R is optionally substituted by

R^U;

Q is optionally hydrido with the proviso that Z is selected from other than a bond;

4a 4b K is CR R ;

4a 4b R and R are independently selected from the group consisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; o 4a 4b 1 1

E , with the proviso that K is CR R , is E wherein E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O),

C(S)N(H), (H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and

C(O)N(H)S(O)₂;

14 K is optionally (CH(R )) -T wherein j is 0 or 1 and T is a bond or

7 14

N(R ) with the proviso that (CH(R )): is bonded to the phenyl ring;

14 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl; o 14 2 2

E , with the proviso that K is (CH(R ));-T, is E wherein E is selected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),

(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Ϊ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g contiguous atoms from the point of attachment of Q to said phenyl or said

heteroaryl to said phenyl or said heteroaryl is substituted by Q , a carbon s 17 adjacent to the point of attachment of Q is optionally substituted by R , g another carbon adjacent to the point of attachment of Q is optionally

substituted by R , a carbon adjacent to Q is optionally substituted by R , b 19 and another carbon adjacent to Q is optionally substituted by R ;

16 17 18 19 R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, nitro, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy, and cyano; 16 19 R or R is optionally selected from the group consisting of

20 21 26 25 23 24 25 23 24

NR R , N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , aminoalkyl,

hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴ with the

20 21 proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time,

23 24 with the further proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, aminoalkyl, amino, dialkylamino, alkylamino, and hydroxyalkyl;

Q is selected from the group consisting of a bond, (CR R )^

14 1 wherein b is an integer selected from 1 through 4, and (CH(R ))_C-W -

(CH(R ))_(j wherein c and d are integers independently selected from 1

1 14 through 3 and W is selected from the group consisting of C(O)N(R ),

(R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the

14 proviso that R is selected from other than halo when directly bonded to N,

37 38 14 and with the additional proviso that (CR R and (CH(R ))_c are bonded to E"

37 38

R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl; 38 38

R is optionally aroyl or heteroaroyl, wherein R is optionally substituted with one or more substituents selected from the group consisting of

16 17 18 19

R , R , R , and R ;

Y is optionally Y wherein Y is Q -Q ;

Y° is optionally Q^b-Q^ss wherein Q^SS is (CH(R¹⁴))_e-W²-(CH(R¹⁵))_h,

2 4a 4b wherein e and h are independently 1 or 2 and W^{^} is CR =CR , with the

14 o proviso that (CH(R ))_e is bonded to E ;

Y° is optionally Q^b-Q^ssss or Q^b-Q^ssssr wherein Q^SSSS is (CH(R³⁸))

W⁵, Q^SSSSr is (CH(R³⁸))_r-W⁶, r is 1 or 2, ⁵ and W⁶ are independently selected from the group consisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyI, 2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo( 1 ,2-a)pyridinyl , 3 ,4-imidazo( 1 ,2-a)pyridinyl, 3 ,5-imidazo( 1 ,2-a)pyridinyl , 3 ,6-imidazo( 1 ,2-a)pyridinyl, 3,7-imidazo(l,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 13-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naρhthyl, 1,7-naphthyl, 1,8-naρhthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl, ,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinohnyl, 3,4-cinnolinyl, 3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl,

5 and each carbon and hyrido containing nitrogen member of the ring of the W

6 5 6 and of the ring of the W , other than the points of attachment of W and W ,

9 10 is optionally substituted with one or more of the group consisting of R , R ,

R , and R , with the proviso that Q is bonded to lowest number substituent

5 b position of each W , with the further proviso that Q is bonded to highest

number substituent position of each W , and with the additional proviso that

(CH(R ))_r is bonded to E .

22. Compound of Claim 21 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substituted by R , the other carbon adjacent to the

carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the 35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q^b;

B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A

•2 γι 1.Λ ^c with one or more of the group consisting of R , R , R , R , and R ;

B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,

33 wherein each ring carbon is optionally substituted with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon

9 13 atom at the point of attachment are optionally substituted with R or R , a ring

9 carbon or nitrogen atom adjacent to the R position and two atoms from the

point of attachment is optionally substituted with R , a ring carbon or nitrogen

13 atom adjacent to the R position and two atoms from the point of attachment

12 is optionally substituted with R , a ring carbon or nitrogen atom three atoms

10 from the point of attachment and adjacent to the R position is optionally

substituted with R , a ring carbon or nitrogen atom three atoms from the 12 point of attachment and adjacent to the R position is optionally substituted

, 33 with R , and a ring carbon or nitrogen atom four atoms from the point of

11 33 attachment and adjacent to the R and R positions is optionally substituted

Q ι r\ 1 1 ι < 1 R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano;

15 7

A is bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1, pa is an integer

7 selected from 0 through 3, and W is selected from the group consisting of O,

S, C(O), (R^?)NC(O), (R^?)NC(S), and N(R^?), with the proviso that W^? is bonded to the N(H) on the 1,4-quinone ring;

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q; o 41 42

Z is selected from the group consisting of a bond, (CR R )_q

41 o 42 wherein q is 1 or 2, and (CH(R ))_g-W -(CH(R ))_p wherein g and p are integers independently selected from 0 through 3 and W^ is selected from the group consisting of O, S, C(O), S(O), N(R⁴¹), and ON(R⁴¹); n 41 22 42 Z is optionally (CH(R ))_e-W -(CH(R ))_h wherein e and h are

independently 0 or 1 and W^{^} is selected from the group consisting of

41 42 CR =CR , 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 13-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,Smorpholinyl, 1,2-piperazinyl, 13-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-ρiperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, l,2-pyrrolidinyl,13-pyrrolidinyl, 23-pyrrolidinyl, 2,4-pyπolidinyl, 2,5-pyrrolidinyl, 3,4-pyπolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,

2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1 ,4-quinone ring and W^ is optionally substituted with one or more

9 10 11 12 13 substituents selected from the group consisting of R , R , R , R , and R ;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and amino;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the carhon at the point of attache is optional ubbed b_y R¹² and an_y

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

Q is optionally hydrido with the proviso that Z is other than a bond; 4 4aa„ 44bb K is CR ;

4a 4b R and R are independently selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl;

Q 4a 4b 1 1

E , with the proviso that K is CR R , is E wherein E is selected from the group consisting of a covalent single bond, C(O)N(H), (H)NC(O),

S(O)₂N(H), and N(H)S(O)₂;

14 K is optionally (CH(R )) -T wherein j is 0 or 1 and T is a bond or

7 14

N(R ) with the proviso that (CH(R ))j is bonded to the phenyl ring;

14 R is hydrido or halo; o 14 2 2

E , with the proviso that K is (CH(R ));~T, is E wherein E is selected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂; ϊ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three s atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

16 b optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ; 16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

NR²°R²¹, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

N(R )C(NR )N(R )(R ), and C(NR )NR R , with the proviso that no

20 21 more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time, with the further proviso that

23 24 no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

20 21 23 24 25 26 R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino;

37 38 Q is selected from the group consisting of a bond, (CR R

14 1 wherein b is an integer selected from 1 through 4, and (CH(R ))_C-W -

(CH(R ))_(j wherein c and d are integers independently selected from 1

1 14 through 3 and W is selected from the group consisting of C(O)N(R ),

(R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the

14 proviso that R is selected from other than halo when directly bonded to N,

37 38 37 38 and with the additional proviso that (CR R )_jj and (CR R , an

(CH(R¹⁴))„ are bonded to E°; 37 38

R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl;

38 38

R is optionally aroyl or heteroaroyl, wherein R is optionally substituted with one or more substituents selected from the group consisting of

„16 17 18 _{ι π}19 R , R , R , and R ;

Y is optionally Y wherein Y is Q -Q ;

Y° is optionally Q^b-Q^SS wherein Q^SS is (CH(R¹⁴))_e-W²-(CH(R¹⁵))_h,

2 4a 4b wherein e and h are independently 1 or 2 and W^{^} is CR =CR with the

14 o proviso that (CH(R ))_e is bonded to E .

23. Compound of Claim 22 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 6 atoms from the point of attachment of B to A with one or more

32 33 34 35 36 of the group consisting of R , R , R , R , and R ;

_^32 „33 34 35 , „36 . , , , ,

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is (CH(R ))_pa-W wherein pa is an integer selected from 0 through

7 7 7

3 and W is selected from the group consisting of O, S, and N(R ) wherein R is hydrido or alkyl;

R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; X is selected from the group consisting of hydrido, alkyl. cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio; R² is Z°-Q; o 41 42

Z is a bond or (CR R )_q wherein q isl or 2;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, and amino;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 1 1 carbon adjacent to both R and R is optionally substituted by R , with the proviso that Q is other than a phenyl when Z is a bond;

9 10 11 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano;

4a 4a

K is CHR wherein R is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E is selected from the group consisting of a bond, C(O)N(H),

(H)NC(O), (R⁷)NS(O)₂, and S(O)₂N(R⁷);

Y is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three

contiguous atoms from the point of attachment of Q to the phenyl or b heteroaryl ring is substituted by Q , a carbon adjacent to the point of s 17 attachment of Q is optionally substituted by R , another carbon adjacent to s 18 the point of attachment of Q is optionally substituted by R , a carbon

adjacent to Q is optionally substituted by R , and another carbon adjacent to

Q is optionally substituted by R ;

16 17 18 1 Q R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; R or R is optionally selected from the group consisting of

NR²°R²¹, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the proviso that no 20 21 more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time and with the further proviso

23 24 that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

20 21 23 24 25 26 R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino; γη o

Q is selected from the group consisting of a bond, (CR R ^ wherein b is an integer selected from 1 through 3, and

14 1 15

(CH(R ))_C-W -(CH(R ))_(j wherein c and d are independently 1 or 2 and

1 14 14 W is selected from the group consisting of C(O)N(R ), (R )NC(O), S(O),

14 14 14 14

S(O)₂, S(O)₂N(R ), N(R )S(O)₂, and N(R ), with the proviso that R is selected from other than halo when directly bonded to N and with the further ι-j O Λ Λ proviso that (CR R )^, and (CH(R ))_c are bonded to E ;

14 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

37 38

R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl;

38 R is optionally aroyl and heteroaroyl;

14.

Y° is optionally Q -Q^SS wherein Q^SS is (CH(R ))_e-W „2 -( ,C_H(_R15 ))_h,

wherein e and h are integers independently selected from 1 through 2 and Mv

4a 14 o is CR =CH with the proviso that (CH(R ))_e is bonded to E .

24. Compound of Claim 23 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, trialkylsilyl, C2-C4 alkyl, C3-C5 alkylenyl, C3-C4 alkenyl, C3-C4 alkynyl, and C2-C4 haloalkyl, wherein each member of group B is optionally substituted at any carbon up to and including 3 atoms from the point of attachment of B to A with one or more

32 33 34 of the group consisting of R , R , and R ;

32 33 34

R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, and cyano;

15 7

A is (CH(R ))_pa-N(R ) wherein pa is an integer selected from 0

7 through 2 and R is hydrido or alkyl;

.15 .

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q;

Z is a bond or CH₂;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 πng to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 1 1 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido, and cyano;

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of attachment of Q is optionally substituted by R , a carbon adjacent to Q is

optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ;

16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

20 21 26 25 23 24 25 23 24 NR R , N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that

20 21 no more than one of R and R is hydroxy at the same time and with the

23 24 further proviso that no more than one of R and R is hydroxy at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g

Q is selected from the group consisting of a bond, CH₂, and CH₂CH .

25. Compound of Claim 24 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of ethyl, 2-propenyl,

2-propynyl, propyl, isopropyl, -CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂-, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, and 2,2-difluoropropyl, wherein each member of group B is optionally substituted at any carbon up to and including 3 atoms from the point of attachment of B to

32 33 34

A with one or more of the group consisting of R , R , and R ;

32 33 34

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, 1,1,2,2-tetiafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano; A is selected from the group consisting of a bond, NH, and N(CH3);

X is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1 -aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q;

Z is a bond or CH ;

Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,

4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-ρyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is

9 optionally substitated by R , the other carbon adjacent to the carbon at the point 13 9 of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by

R , a carbon adjacent to R and two atoms from the carbon at the point of

12 attachment is optionally substituted by R , and any carbon adjacent to both

10 12 11 R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl,

N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-ρhenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-isopropylamidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanoρyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylρhenoxy, 4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy,

4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-ρhenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulf onyl, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, 4-tiifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3 ,5-bis-trifluoromethylbenzyloxy , 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4- trifluoromethyl thiobenzyloxy, 2,3 ,4-trifluorophenoxy , 2,3 ,5-trifluorophenoxy , 3-pentafluoroethylphenoxy,

3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy; i is selected from the group consisting of: l-Q^b.4-Q^S-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine, 3-Q -6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-6-R¹⁸pyrazine,

3-Q^b-6-Q^S-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,

„ _^b „ s _Λ „ 17 _^ 18 . . ,. , _Λb _{Λ ^}s _Λ , 16 _^ 19 .

2-Q -5-Q -4-R -6-R pyπmidine, 5-Q -2-Q -4-R -6-R pyπmidme, b „ _^s , _ 16 _ „ 19 , . „ _{Λ Λ}b „ s _ „ 16 „ _ 17 , .

3-Q -5-Q -4-R -2-R thiophene, 2-Q -5-Q -3-R -4-R thiophene,

3-Q -5-Q^S-4-R -2-R furan, 2-Q -5-Q -3-R -4-R furan,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹pyπole, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷pyπole, b s 19 b s 17

4-Q -2-Q -5-R imidazole, 2-Q -4-Q -5-R imidazole,

_{Λ ^}b , _Λs , „16. , „ b „ _Λs _Λ 16.

3-Q -5-Q -4-R isoxazole, 5-Q -3-Q -4-R isoxazole, b s 16 b s 19

2-Q -5-Q -4-R pyrazole, 4-Q -2-Q -5-R thiazole, and

2-Q -5-Q^S-4-R thiazole;

16 π 15? 1 Q

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R or R is optionally selected from the group consisting of

20 21 26 25 23 24 25 23 24

NR R , N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, s ^ /^ O^s O¹^ OΔ

C(NR )NR R , and N(R )C(NR )N(R )(R ), with the proviso that 20 21 23 24 no more than one of R , R , R , and R can be hydroxy, when any two

20 21 23 24 of the group consisting of R , R , R , and R are bonded to the same

^■ atom and with the further proviso that said Q group is bonded directly to a carbon atom;

20 21 23 _^24 25 , „26 . , _J , , R , R , R , R , R , and R are independently selected irom the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy;

Q is selected from the group consisting of a bond, CH₂, and CH₂CH₂.

26. Compound of Claim 24 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

A is selected from the group consisting of CH2N(CH3),

CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃);

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1 -aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1 -hydroxyethyl, 2-hy droxy ethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q;

,o .

Z is a bond or CH ; Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, Sisoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-ρyrimidinyl, 4-pyrimidinyl, Spyrimidinyl, 3-pyridazinyl, 4-pyridazinyi, and l,3,Striazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is

9 optionally substituted by R , the other carbon adjacent to the carbon at the point

13 9 of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of

anactaen, is optional substitated b_y R¹², and a„_y carbon adjacent to both

10 12 11

R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,

N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetiafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl,

2,2,2-trifluoro-l-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,

N,N-dimethylamidocarbonyl, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetarnido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, NJN-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-isopropylamidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-cMoro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenyl amino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2, difluorobenzyloxy, 3,5-difluoroρhenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,

3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro- trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy,

2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylρhenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxy phenoxy, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylρhenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy , 2,3 ,4-trifluorophenoxy , 2,3 ,5-trifluorophenoxy , 3-ρentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy; Y is selected from the group consisting of:

1-Q -4-Q^S-2-R -3-R -5-R -6-R benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-6-R¹⁸pyrazine,

„ > _{^ ^}s „ 18 _ 18 19 . , . 3-Q -6-Q -2-R -5-R -4-R pyπdazme,

2-Q -5-Q^S-4-R -6-R pyrimidine, 5-Q -2-Q^S-4-R -6-R pyrimidine,

3-Q -5-Q^S-4-R -2-R thiophene, 2-Q -5-Q^S-3-R -4-R thiophene,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹furan, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷furan,

„ b _ _Λs _Λ 16 _Λ 19 „ ,__. o „ _Λs „ 16 , , 17

3-Q -5-Q .4-R -2-R pyπole, 2-Q -5-Q -3-R -4-R pyπole, b s 19 b s 17

4-Q -2-Q -5-R imidazole, 2-Q -4-Q -5-R imidazole,

3-Q -5-Q^S-4-R isoxazole, 5-Q -3-Q^S-4-R isoxazole,

,, _^b _ _^s „ 16 , , _^b „ _^s _ _ 19 , .

2-Q -5-Q -4-R pyrazole, 4-Q -2-Q -5-R thiazole, and

2-Q -5-Q^S-4-R thiazole;

16 17 18 , „19 . _Λ , , , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,

1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; b 20 21

Q is selected from the group consisting of NR R ,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that

20 21 23 24 no more than one of R , R , R , and R can be hydroxy, when any two

20 21 23 24 of the group consisting of R , R , R , and R are bonded to the same

atom, and with the further proviso that said Q group is bonded directly to a carbon atom;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy; Q is selected from the group consisting of a bond, CH₂, and CH₂CH₂.

27. Compound of Claim 26 or a pharmaceutically acceptable salt thereof, wherein;

A is selected from the group consisting of CH₂N(CH3),

CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃);

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro; R² is Z°-Q;

Z is a bond or CH₂;

Q is selected from the group consisting of 3-amidocarbonyl-5-aminophenyl, 3-amino- (N-benzylamidocarbonyl)ρhenyl, 3-amino-5-benzylphenyl, 3-amino-5-(2-phenylethyl)phenyl, 3-amino-5-benzylaminophenyl, 3-amino-5-(2-phenylethylamino)ρhenyl, 3-amino-5-benzyloxyphenyl, 3-amino-5-(2-phenylethoxy)phenyl, 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino- (N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, 3-amino- (N-(l-methyl-l-phenylethyl)amidocarbonyl)ρhenyl, 3-amino-5-(N-benzylamidosulfonyl)phenyl, 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl, 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylρhenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,

3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyρhenyl, 3-carboxy- hydroxyρhenyl, 3-amino- carboxy phenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-hydroxy phenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminoρhenyl, 2-methylρhenyl, 3-methylphenyl, 4-methyiphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-ρyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;

Y is selected from the group consisting of:

, 1-Qb -4 „_Q _Λs _ „_R 16 _ „3_R 11 -5 „_ „R18 -6 „- „R19, benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine, ^ „ s „ 16 _ 18 _Λ „ 19 . ,. 3-Q -6-Q -2-R -5-R -4-R pyridine, b s 16 19 b s 16 17 3-Q -5-Q -4-R -2-R thiophene, and 2-Q -5-Q -3-R -4-R thiophene; R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano;

Q^b is C(NR²⁵)NR²³R²⁴;

23 24 25

R , R , and R are independently selected from the group consisting of hydrido and methyl;

Q^s is CH₂.

28. A compound as recited in Claim 27 or a pharmaceutically acceptable salt thereof where said compound is selected from the group consisting of:

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]- 6- [N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl]]acetamide; 2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-6-

[N-ethyl-N-methylhydrazino]- 1 ,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]-5- chloro-6-[N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl] jacetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-aminophenyl]- chloro-6-[N-ethyl-N-methylhydrazino]-l,4-benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]- 6-[N,N-dimethylhydrazino]-l,4-benzoquinonyl]]acetamide;

2-[2-[N-[[ aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]- 6-[N-ethyl-N-methylhydrazinoj- 1 , benzoquinonyl] jacetamide; 2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3,5-diaminophenyl]- chloro-6-[N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl]]acetamide;

2-[2-[N-[[ amdnoiminomethylρhenyl]methyl]-3-[3,5-diaminophenyl]- 5-chloro-6-[N-ethyl-N-methylhydrazino]-l,4-benzoquinonyl]]acetamide; 2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5- carboxyphenyl]- 6-[N,N-dimethylhydrazino]- 1 ,4-benzoquinonyl]3acetamide; 2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-S carboxyphenyl]-6-[N-ethyl-N-methylhydrazino]- 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino- carboxy ρhenyl]-5-chloro-6- [N,N-dimethylhy drazino]- 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino- carboxyρhenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]- 1 ,4- benzoquinonyl]]acetamide; 2-[2-[N-[[4-aminoiminomethylρhenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]- 6- [N,N-dimethylhy drazino 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]-6-[N-ethyl-N-methylhydrazino]- 1 ,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]-5-chloro-6-[N,N-dimethylhydrazino]-l,4- benzoquinonyl]]acetamide;

2-[2-[N-[[4-aminoiminomethylphenyl]methyl]-3-[3-amino-5-(N- benzylamidocarbonyl)phenyl]-5-chloro-6-[N-ethyl-N-methylhydrazino]-l,4- benzoquinonyl]]acetamide.

29. Compound of Claim 22 or a pharmaceutically acceptable salt thereof, wherein;

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl 32 ring to A is optionally substitated by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substitated by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substitated by R , a carbon adjacent to R and two atoms from the

carbon at the point of attaint is o_P-onail_y snbstiMed b_y R³⁵, and an_y

33 35 34 carbon adjacent to both R and R is optionally substitated by R ;

32 33 34 35 , 36 . _J _, , , R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1, pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, W -

42 o

(CH(R ))_p wherein p is 0 or 1 and W is selected from the group consisting

of O, S, and N(R⁴¹);

41 42

R and R are independently hydrido or alkyl; Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substitated by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substitated by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substitated by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido, and cyano;

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralJkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substitated by Q , a carbon two or three

atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substitated by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substitated by R , another carbon adjacent to the point of

attachment of Q is optionally substitated by R , a carbon adjacent to Q is

optionally substituted by R is optionally

19 substitated by R ;

Λ s 1 *7 1 Q "l O

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

16 19 20 21 25 23 24

R or R is optionally NR R or C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

25 23 24 20 21

C(NR )NR R , with the proviso that no more than one of R and R is

23 hydroxy at the same time and with the further proviso that no more than one of R

24 and R is hydroxy at the same time;

20 21 23 24 25

R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g

Q is selected from the group consisting of a bond, CH₂, and CH₂CH₂.

30. Compound of Claim 29 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-ρyridyl, 4-pyridyl, 2-ρyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-ρyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to A is

32 optionally substitated by R , the other carbon adjacent to the carbon at the

point of attachment is optionally substitated by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally

33 36 substitated by R , a carbon adjacent to R and two atoms from the carbon at

35 the point of attachment is optionally substituted by R , and any carbon

33 35 34 adjacent to both R and R is optionally substitated by R ;

32 33 34 35 36 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and Q^b;

A is selected from the group consisting of a bond, NH, N(CH₃),

N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,

C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, 0,

S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂;

Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-ρyrazinyl, 2-ρyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1 ,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is

9 optionally substituted by R , the other carbon adjacent to the carbon at the point

13 9 of attachment is optionally substitated by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substitated by

10 13

R , a carbon adjacent to R and two atoms from the carbon at the point of

12 attachment is optionally substitated by R , and any carbon adjacent to both

10 12 11 R and R is optionally substitated by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hy droxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l -hydroxyethyl, methoxy carbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy , benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylρhenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanoρyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3 ,5-difluorophenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, ,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,

3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fiuorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluoroρhenoxy, 2-fluoro-3-trifluoromethylphenoxy,

2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylρhenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulfonyl, 3-trifluoromefhoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromefhoxyρhenoxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3 ,5-bis-trifluoromethylbenzyloxy , 4-trifluoromethylρhenoxy , 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy , 2,3 ,4-trifluorophenoxy , 2,3 ,5-trifluorophenoxy , 3-pentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy;

Y is selected from the group consisting of: l_Q^b-4-Q^S_₂-R¹⁶-3-R¹⁷_5_R¹⁸_6-R¹⁹benzene,

_Λ ^b _{e ^}s 17 _Λ % _n 19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyπdme,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-6-R¹⁸pyrazine,

3-Q^b-6-Q^S-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,

2-Q^b-5-Q^S-4-R¹⁷-6-R¹⁸pyrimidine, 5-Q^b-2-Q^S-4-R¹⁶-6-R¹⁹pyrimidine,

3-Q -5-Q^S-4-R -2-R thiophene, 2-Q -5-Q^S-3-R -4-R thiophene,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹furan, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷furan,

3-Q -5-Q^S-4-R -2-R pyπole, 2-Q -5-Q^S-3-R -4-R pyπole, b s 19 b s 17 4-Q -2-Q -5-R imidazole, 2-Q -4-Q -5-R imidazole,

3-Q -5-Q^S-4-R isoxazole, 5-Q -3-Q^S-4-R isoxazole, b s 16 b s 19

2-Q -5-Q -4-R pyrazole, 4-Q -2-Q -5-R thiazole, and

■t -t η

2-Q -5-Q^S-4-R thiazole;

16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluσroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1 -hydroxyethyl, 2-hy droxy ethyl, and cyano;

R

19 b

R , and Q are not simultaneously hydπdo; b 25 23 24 Q is C(NR )NR R or hydrido, with the proviso that no more than

23 24 one of R and R is hydroxy at the same time;

23 24 25 , .

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, and hydroxy; s Q is selected from the group consisting of a bond, CH₂ and CH₂CH .

31. Compound of Claim 30 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of 2-aminophenyl,

3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyρhenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chloroρhenyl,

3,4-dichlorophenyl, 2-fiuorophenyl, 3-fluorophenyl, 3,4-difluorophenyl,

3-hydroxyphenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl,

3-methoxyphenyl, 4-methoxyρhenyl, 3-methylphenyl, 4-methylρhenyl, phenyl,

3-trifluoromethylρhenyl, 2-imidazoyl, 2-pyridyl, 3-ρyridyl, 5-chloro-3-trifluoromethyl-2~pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, and

3-trifluoromethyl-2-pyridyl ;

A is selected from the group consisting of CH₂, CH₃CH, CF₃CH,

NHC(O), CH₂CH₂, and CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, 0, S, NH, N(CH₃), OCH₂, and SCH₂;

Q is selected from the group consisting of

3-amidocarbonyl- aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-benzylphenyl, 3-amino-5-(2-phenylethyl)phenyl,

3-amino-5-benzylaminophenyl , 3-amino- (2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl, 3-amino- (2-phenylethoxy)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-( 1 -phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-benzylamidosulfonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)ρhenyl,

3-amino-5-(N-ethylamidocarbonyl)phenyl,

3-amino- (N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl ,

3-amino-5-(N-isobutylamidocarbonyl)phenyl,

3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,

3-amino-5-(N-cyclobutylamidocarbonyl)ρhenyl,

3-amino- (N-cycloρentylamidocarbonyl)ρhenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl,

3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, amino-2-methylthioρhenyl, 3-aminophenyl, 3-amino-5-(4-trifluoromethylbenzylamino)phenyl, 3-amino-5-(4-trifIuoromethylbenzyloxy)phenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyρhenyl, 3-amino-5-carboxyphenyl, 3-chloroρhenyl ,

2-chlorophenyl, 3-cyanophenyl, 3, diaminophenyl, 3-dimethylarninophenyl, 2-fluoroρhenyl, 3-fluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylρhenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-ρyridyl, 2-thienyl, and 3-thienyl; ϊ is selected from the group consisting of:

1 , -Q _^b .4 _Λ-Q s _ _Λ2_ „R16. _n3-R 11 _5 _e-R 18 -6 „- „R19, benzene,

_« ^^b _e s _^ 17 _Λ 18 „ „ 19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyπdine, Λb „ _^s _Λ „ 16 _ _ 18 „ „19

3-Q -6-Q -2-R -5-R -4-R pyπdine,

_, > _ _^s , _ 16 19 , . „ , _{Λ Λ}b _ _Λs _Λ „ 16 _ _^ 17 , . _

3-Q -5-Q -4-R -2-R thiophene, and 2-Q -5-Q -3-R -4-R thiophene;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

16 1 O 03 OΔ f R or R is optionally C(NR )NR R with the proviso that R ,

R , and Q are not simultaneously hydrido;

17 18 R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q^b is C(NR²⁵)NR²³R²⁴ or hydrido;

23 24 25

R , R , andR are independently hydrido or methyl;

Q is CH₂.

2. Compound of Claim 29 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substitated by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substitated by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

33 36 optionally substituted by R , a carbon adjacent to R and two atoms from the

35 carbon at the point of attachment is optionally substitated by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_n wherein π is 0 or 1, pa is an

7 7 integer selected from 0 through 3, and W is N(R );

7 R is hydrido or alkyl;

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl; X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q; Z is a bond;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substitated by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substitated by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substitated by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano;

Y is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substitated by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is 17 optionally substitated by R , another carbon adjacent to the point of

attachment of Q is optionally substitated by R , a carbon adjacent to Q is

16 b optionally substitated by R , and another carbon adjacent to Q is optionally

19 substitated by R ;

16 17 18 19 . , , , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

16 19 20 21 25 23 24 R or R is optionally NR R or C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

25 23 24 C(NR )NR R ;

20 21 23 24 25

R , R ,R , R , and R are independently hydrido or alkyl;

Q^S is CH₂.

33. Compound of Claim 32 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substitated by R , the other carbon adjacent to the

36 carbon at the point of attachment is optionally substitated by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

33 36 optionally substitated by R , a carbon adjacent to R and two atoms from the 35 carbon at the point of attachment is optionally substitated by R , and any

33 35 34 carbon adjacent to both R and R is optionally substituted by R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, _ amidocarbonyl, carboxy, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH₃), CH₂,

CH₃CH, and CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro;

2 R is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyπolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-ρyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to the 1,4-quinone ring is optionally substituted by

9

R , the other carbon adjacent to the carbon at the point of attachment is

13 9 optionally substituted by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is optionally substitated by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment is

12 10 12 optionally substituted by R , and any carbon adjacent to both R and R is

11 optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;

R and R are independently selected from the group consisting of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, carboxy, carboxy methyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifiuoroacetamido, aminomethyl, N-methylamino, dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and cyano; Ϊ is selected from the group consisting of:

, > _{Λ Λ}s „ 16 „ 17 _e „18 „ 19,

1-Q -4-Q _₂-R -3-R _5-R -6-R benzene,

„ _^b _{e ^}s , 17 _Λ 18 19 . ,. „ Jo _ s „ „16 _Λ L1 _Λ . , 2-Q -5-Q -6-R -4-R -3-R pyπdine, 2-Q -5-Q -3-R -4-R thiophene,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹furan, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷furan,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹pyπole, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷pyπole, b s 19 b s 17

4-Q -2-Q -5-R thiazole, and 2-Q -5-Q -4-R thiazole;

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano; b 20 21 25 23 24

Q is NR R or C(NR )NR R ;

20 21 _π23 24 _{J π}25 . _{J Λ} , , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl; Q^s is CH₂.

34. Compound of Claim 33 or a pharmaceutically acceptable salt thereof, wherein; B is selected from the group consisting of 2-aminophenyl,

3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichloroρhenyl, 2-fluorophenyl, 3-fluoroρhenyl, 3,4-difluorophenyl, 3-hydroxyρhenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazoyl, 2-pyridyl, 3-pyridyl, 5-chloro-3-trifluoromethyl-2-ρyridyl, 4-ρyridyl, 2-thienyl, 3-thienyl, and 3-trifluoromethyl-2-pyridyl ;

A is CH₂ or CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;

R is selected from the group consisting of 3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)ρhenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-benzylamidosulfonyl)phenyl, 3-amino- (N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)amidocarbonyl)ρhenyl , 3-amino-5-(N-cyclobutylamidocarbonyl)ρhenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3 -carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxyρhenyl, 3-carboxymethyl-5-aminoρhenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyρhenyl, 3-methoxyaminoρhenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylρhenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-ρyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;

Y is selected from the group consisting of:

_« ^b _Λ s _Λ 16 _n 17 _e „18 „ 19,

1-Q -4-Q -2-R -3-R -5-R -6-R benzene,

~ _^b _{e Λ}s _^ 17 _Λ 18 „ 19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyridine,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene, and 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷thiophene;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

17 18 R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q is C(NR )NR R ;

23 24 25

R , R , and R are independently hydrido or methyl;

Q^S is CH₂.

35. Compound of Claim 34 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl, phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and 3-trifluoromethyl-2-ρyridyl ;

A is CH₂ or CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro; p R is selected from the group consisting of

3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,

3-amino- (N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino- (N-(l-phenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-methyl-l-ρhenylethyl)amidocarbonyl)ρhenyl,

3-amino-5-(N-benzylamidosulfonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)ρhenyl,

3-amino-5-(N-ethylamidocarbonyl)ρhenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl,

3-amino-5-(N-propylamidocarbonyl)ρhenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)aιnidocarbonyl)phenyl, 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,

3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 3-aminophenyl, 3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl, -dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, -methylaminophenyl, 2-methylphenyl, 3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl;

Y is selected from the group consisting of 5-amidino-2-thienylmethyl,

4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amdinobenzyl.

36. Compound of Claim 29 where said compound is selected from the group of the Formula:

or a pharmaceutically acceptable salt thereof, wherein B, A, R ,X°, andY are selected to form a compound selected from the group consisting of;

R 2 is 3-aminophenyl, B is phenyl, A is CH₂, Y 0 is 4-amidinobenzyl, and

X is chloro; p 0

R is 3-aminophenyl, B is 3 -chlorophenyl, A is CH₂CH , Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is phenyl, A is CH₂, Y is 4-amidinobenzyl, and

X^u is hydrido;

7 0

RR² iiss 33-aminophenyl, B is 2-imidazoyl, A is CH CH₂CH₂, Y is 4- amidinobenzyl, and X is chloro;

2

R is 3-amidocarbonyl-5-aminophenyl, B is 3-chloroρhenyl, A is CH₂CH₂, i is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is chloro; 2 R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is 3- chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is chloro; p

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)ρhenyl, B is 3- chlorophenyl, A is CH CH₂, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)- phenyl, B is

3-chlorophenyl, A is CH CH₂, Y is 4-amidinobenzyl, and X is chloro;

2 0 .

R is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH CH₂,Y is 4- amidinobenzyl, and X is chloro;

R is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH CH , Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amidocarbonyl- aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, ϊ is 4-amidinobenzyl, and X is hydrido;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is hydrido;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is 3- chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is hydrido;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)ρhenyl, B is 3- chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is hydrido;

2

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)- phenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y is 4-amidinobenzyl, and X is hydrido;

7 0

R is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH₂CH , Y is 4- amidinobenzyl, andX is hydrido; and

2 0

R is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH CH₂,Y is

4-amidinobenzyl, and X is hydrido.

7. Compound of Claim 22 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substitated at any carbon up to and including 6 atoms from the

32 point of attachment of B to A with one or more of the group consisting of R ,

33 34 35 , „36 R , R , R , and R ;

32 " 3 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R )) _a-(W )_rr wherein rr is 0 or 1, pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q; Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, W -

42 o

(GH(R )) wherein p is 0 or 1 and W is selected from the group consisting

of O, S, and N(R⁴¹);

41 42

R and R are independently hydrido or alkyl; Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substitated by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substitated by R , and any

10 12 11 carbon adjacent to both R and R is optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano; i is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substitated by R , another carbon adjacent to the point of

attachment of Q is optionally substitated by R , a carbon adjacent to Q is

16 optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ;

16 17 1 R 10

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

20 21 _τ/„26_{^/ m}25 _τ/„23 _r,24 , _^ 25, 23 24 . , _Λ NR R , N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b . , . . _{r m}20 21 ,

Q is selected from the group consisting of NR R , hydπdo,

25 23 24 26 25 23 24 C(NR )NR R , and N(R )C(NR )N(R )(R ), with the proviso that

20 _{j n}21 , , , , . _J . , , no more than one of R and R is hydroxy at the same time and with the

23 24 further proviso that no more than one of R and R is hydroxy at the same time; 20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g

Q is selected from the group consisting of a bond, CH₂, and

CH CH₂.

38. Compound of Claim 37 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propynyl, 2-proρenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-ρentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, l-methyl-2-butenyl, l-methyl-3-butenyl, l-methyl-2-butynyl, 3-pentyl, l-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-4-ρentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3-hexyl, l-ethyl-2-butenyl, l-ethyl-3-butenyl, l-propyl-2-propenyl, l-ethyl-2-butynyl, 1-heρtyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-5-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-meιhyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-ρentenyl, l-ethyl-4-pentenyl, l-butyl-2-propenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoroproρyl, 4-trifluoromethyl- 5,5,5-trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and

333-trifluoropropyl, wherein each member of group B is optionally substitated at any carbon up to and including 5 atoms from the point of attachment of B to

. ■ , . , ■ ■ _r„32 _π33 34 35 36

A with one or more of the group consisting of R , R , R , R , and R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3 -pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l -hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,

N,N-dimethylamidocarbonyl, cyano, and Q ;

A is selected from the group consisting of bond, NH, N(CH₃), N(OH),

CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃),

CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1 -aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy, 1,1,2,2-tetiafluoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, 0, S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂;

Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-ρyridazinyl, and 13,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or o 9 heteroaryl ring to Z is optionally substituted by R , the other carbon adjacent

to the carbon at the point of attachment is optionaily substituted by R¹³, a

9 carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substitated by R , a carbon adjacent to R and two atoms from

12 the carbon at the point of attachment is optionally substitated by R , and any

10 12 11 carbon adjacent to both R and R is optionally substitated by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hy droxy ethyl, 2,2,2-trifluoro-l-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl,

2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifIuoromethylbenzyI)arnidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-( 1 -methyl- l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmefhoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluoroρhenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl, 5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3 ,4-difluorobenzyloxy, 2,5-difluorobenzyloxy,

3 ,5-difluorophenoxy , 3 ,5-difluorobenzyloxy , 4-difluoromethoxybenzyloxy, 2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3 ,5-dimethylphenoxy, 3 ,4-dimethylphenoxy, 3 ,4-dimethylbenzyloxy , 3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluorobenzyloxy,

2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro- trifluoromethylbenzyloxy, 4-fluoro-2-trifluoromethylbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylρhenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy ,

4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulf onyl, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy , 2,3 ,4-trifluorophenoxy , 2,3 ,5-trifluorophenoxy ,

3-pentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy;

Y is selected from the group consisting of: l-Q^b-4-Q^S-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene, 2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-6-R^lδpyrazine,

3-Q -6-Q^S-2-R -5-R -4-R pyridazine,

„ _^ , _^s „ 17 _^ 18 . . ,. „ Jo _{Λ ^}s _Λ 16 _^ 19 .

2-Q -5-Q -4-R -6-R pyπrmdme, 5-Q -2-Q -4-R -6-R pyπmidme,

3-Q -5-Q^S-4-R -2-R thiophene, 2-Q -5-Q^S-3-R -4-R thiophene, b s 16 19 b s 16 17

3-Q -5-Q -4-R -2-R furan, 2-Q -5-Q -3-R -4-R furan,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹pyrrole, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷pyπole, b s 19 b s 17

4-Q -2-Q -5-R imidazole, 2-Q -4-Q -5-R imidazole, b s 16 b s 16

3-Q -5-Q -4-R isoxazole, 5-Q -3-Q -4-R isoxazole, b s 16 b s 19 2-Q -5-Q -4-R ρyrazole, 4-Q -2-Q -5-R thiazole, and

2-Q -5-Q^S-4-R thiazole;

„16 17 „18 19 . , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafiuoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, and cyano; x,16 „19 . . „ , . . _{^ τ}„ 0_π21

R or R is optionally selected from the group consisting of NR R ,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that R¹⁶,

19 h

R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that no

20 21 more than one of R and R is hydroxy at the same time and with the further

23 24 proviso that no more than one of R and R is hydroxy at the same time;

20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy;

Q is selected from the group consisting of a bond, CH₂, and CH₂CH₂.

39. Compound of Claim 38 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-proρenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, l-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxyproρyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl;

A is selected from the group consisting of a bond, CH2, NHC(O),

CH₂CH₂, CH₂CH₂CH₂, and CH₃CHCH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro;

R² is Z°-Q;

Z is selected from the group consisting of a bond, CH , 0, S, NH,

N(CH₃), OCH₂, and SCH₂; Q is selected from the group consisting of

3-amidocarbonyl-Saminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-benzylphenyl, 3-amino-5-(2-phenylethyl)phenyl,

3-amino-5-benzylaminophenyl, 3-amino- (2-phenylethylamino)phenyl, 3-amino-5-benzyloxyphenyl, 3-amino-5-(2-phenylethoxy)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,

3-amino- (N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-( 1 -phenyl ethyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl,

3-amino- (N-benzylamidosulfonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,

3-amino-5-(N-ethylamidocarbonyl)phenyl,

3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl,

3-amino-5-(N-isobutylamidocarbonyl)phenyl,

3-amino- (N-(2-butyl)amidocarbonyl)phenyl,

3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,

3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, 3 -amino-5-(N-cy clohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl ,

3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,

3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,

3-aminoρhenyl, 3-amino-5-(4-trifluoromethylbenzylamino)phenyl,

3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyI, 3-amino-5-carboxyphenyl, 3-chlorophenyl,

2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluoroρhenyl, 3-fluorophenyl, 2-hydroxyρhenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminoρhenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidoρhenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; i is selected from the group consisting of: l-Q^b-4-Q^S-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,

_Λ ^ _{r r} > _^ „ 17 „ „ 18 19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyridine, ^_^ ^s _^ „ 16 _r „ 18 „ 19 . ,. 3-Q -6-Q -2-R -5-R -4-R pyridine,

3-Q -5-Q^S-4-R -2-R thiophene, and 2-Q -5-Q^S-3-R -4-R thiophene;

16 19

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

_T ¹⁶ „ 19 . . „ _, _m25 _m23„24 . , , . , _ 16

R or R is optionally C(NR )NR R with the proviso that R ,

19 b

R , and Q are not simultaneously hydrido;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q^b is C(NR²⁵)NR²³R²⁴ or hydrido;

23 24 25

R , R , and R are independently hydrido or methyl;

Q^S is CH₂.

40. Compound of Claim 37 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substitated at any carbon up to and including 6 atoms from the 32 point of attachment of B to A with one or more of the group consisting of R ,

33 34 35 36

R , R , R , and R ;

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1 , pa is an

7 7 integer selected from 0 through 3, and W ιs N(R );

7 R is hydrido or alkyl;

15 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q;

Z is a bond;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substituted by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is opuonaUy substituted by R¹² and any

10 12 11 carbon adjacent to both R and R is optionally substitated by R ; 9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

10 12 R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano; r is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substitated by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substituted by R , another carbon adjacent to the point of s 18 b attachment of Q is optionally substitated by R , a carbon adjacent to Q is

16 h optionally substituted by R , and another carbon adjacent to Q is optionally

19 substituted by R ;

16 17 18 19 . , , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

_»m20 21 _T „26^_/X 25_{N T/T},23 24 _{J m}25, _m23„24 . _L , NR R ,N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido,

N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴;

20 21 23 24 25 , 26 . , , , , , . , R , R , R , R , R , and R are independently hydπdo or alkyl;

Q^S is CH₂.

41. Compound of Claim 40 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-2-pentynyl, l-methyl-3-ρentynyl, 3-hexyl, l-ethyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl,

2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl , 4-trifluoromethyl-5,5,5-trifluoropentyl,

4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 3,3,3-tiifluoropropyl, wherein each member of group B is optionally substitated at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more

^{* *}^^ ^ Δ ' Gi of the group consisting of R , R , R , R , and R ;

32 33 34 35 36 R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q ; A is selected from the group consisting of a bond, NH, N(CH ), CH₂,

CH₃CH, and CH₂CH₂;

A is optionally selected from the group consisting of CH₂N(CH₃),

CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that B is hydrido;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro;

2 R is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-ρyπolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to the 1,4-quinone ring is optionally substitated by

9 R , the other carbon adjacent to the carbon at the point of attachment is

13 9 optionally substituted by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is optionally substitated by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment is

12 10 12 optionally substituted by R , and any carbon adjacent to both R and R is

11 optionally substituted by R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;

10 12 R and R are independently selected from the group consisting of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-( l-phenylethyl)amidocarbonyl , N-( 1 -methyl- 1 -phenylethyl)amidocarbonyl , N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,

N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino, dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and cyano; ϊ is selected from the group consisting of: b _. _Λs 17 „ „ 18 „ „ 19 . ,. „ Jo _ s _ _n 16 „ „ 17 , . „

2-Q -5-Q -6-R -4-R -3-R pyridine, 2-Q -5-Q -3-R -4-R thiophene, b s 16 18 19 b s 16 19

₃_Q -6-Q -2-R -5-R -4-R pyridine, 3-Q -5-Q -4-R -2-R thiophene,

„ b „ s _Λ 16 _Λ „ 19_ „ _Λb _ _ s „ 16 „ _^ ι7„ 3-Q -5-Q -4-R -2-R furan, 2-Q -5-Q -3-R -4-R furan,

„ b _ s , 16 19 , „ Jo „ _^s _n 16 , 11

3-Q -5-Q -4-R -2-R pyπole, 2-Q -5-Q -3-R -4-R pyπole, b s 19 b s 17 4-Q -2-Q -5-R thiazole, and 2-Q -5-Q -4-R thiazole;

16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifiuoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano;

Q is selected from the group consisting of NR R ,

C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴); 20 21 23 24 25 26

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl;

Q^S is CH₂.

42. Compound of Claim 41 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, l-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl;

A is selected from the group consisting of a bond, CH₂, CH₃CH, and

CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;

2 R is selected from the group consisting of

3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl,

3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-benzylamidosulf onyl)phenyl ,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3 -amino-5-(N-(2-butyl)amidocarbonyl)phenyl , 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cycloρentylamidocarbonyl)phenyl,

3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3 -carboxyphenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl , 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hy droxy phenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; i is selected from the group consisting of:

, _^b _Λ s „ 16 „ 11 _^ % „ 19,

1-Q -4-Q -2-R -3-R -5-R -6-R benzene,

„ ^b _e s _^ 17 _Λ 18 „ _π19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyπdine,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene, and 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷thiophene;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; b 25 23 24

Q is C(NR )NR R ;

23 24 25

R , R , and R are independently hydrido or methyl;

Q^s is CH₂.

43. Compound of Claim 42 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, l-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl;

A is selected from the group consisting of a bond, CH2, CH₃CH, and

CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro;

2 R is selected from the group consisting of

3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyI)phenyl, 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-( 1-methyl- 1 -phenylethyl )amidocarbonyl)phenyl, 3-amino-5-(N-benzylamidosulfonyl)phenyl, 3-amino- (N-(2-chlorobenzyl)amidosulfonyl)phenyl,

3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino- (N-(2-butyl)amidocarbonyl)phenyl, 3-amino- (N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 3-aminophenyl, 3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl, 3-dimethylaminoρhenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, phenyl, 3-trifluoroacetømidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; i is selected from the group consisting of 5-amidino-2-thienylmethyl,

4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amidinobenzyl.

44. Compound of Claim 37 where said compound is selected from the group of the Formula:

or a pharmaceutically acceptable salt thereof, wherein B, A, R ,X , andY are selected to form a compound selected from the group consisting of;

7 0

R is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is (S)-2-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

7 0

R is 5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro; R 7 is 2-methyl-3-ammophenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

7 0 .

R is 3-aminophenyl, B is ethyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro; R 7 is 3-aminophenyl, B is ethyl, A is a bond, Y o is 4-amidino-2- fluorobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 2-propenyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R 7 is 3-aminophenyl, B is isopropyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X° is chloro;

R 7 is 3-aminophenyl, B is isopropyl, A is a bond, Y 0 is 4-amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is 2-butyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro;

7 0 R is 3-aminophenyl, B is (R)-2-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 2-propynyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 3-pentyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

2 0

R is 3-aminophenyl, B is hydrido, A is CH₂,Y is 4-amidinobenzyl, and

X is chloro;

R is 3-aminophenyl, B is ethyl, A is CH , Y is 4-amidinobenzyl, and X is chloro;

7 0 R is 3-aminophenyl, B is 2-methypropyl, A is a bond, Y is 4- amidinobenzyl, andX is chloro; R 7 is 3-aminophenyl, B is 2-propyl, A is CH CH, Y 0 is 4-amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is propyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

7 o

R is 3-aminophenyl, B is tert-butyl, A is a bond, Y is 4-amidinobenzyl, and X is hydrido;

7 0

R is 3-aminophenyl, B is tert-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 3-hydroxypropyl, A is a bond, Y is 4- amidinobenzyl, andX is chloro;

2 0

R is 3-aminophenyl, B is 2-methylpropyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro; R 2 is 3-aminophenyl, B i •s butyl, A is a bond, Y 0 is 4-amidinobenzyl, and

X is chloro;

7 0

R is 3-aminophenyl, B is l-methoxy-2-propyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

7 o

R is 3-aminophenyl, B is 2-methoxy ethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

7 0

R is 3-aminophenyl, B is 2-propyl, A is a bond, Y is 5-amidino-2- thienylmethyl, and X is chloro;

R 7 is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond, Y o is 4- amidinobenzyl, and X is chloro;

7 o R is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro; 2 • 0

R is 3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

R 2 is 3-aminophenyl, B is isopropyl, A is a bond, Y 0 is 4-amidinobenzyl, and X is bromo; R 2 is 3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzyl-N-methylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2

R is 3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2

R is 3-amιno-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,

A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amιno-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)ρhenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro; 2

R is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2

R is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4~amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

R is 3-amino-5-(N-( 1,2,3 ,4-tetrahydronaρhth-2-ylmethyl)amidocarbonyl)- phenyl, B is isopropyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 0

R is 3-aminophenyl, B is 2-propyl, A is a bond, Y is 4-amidino-3- fluorobenzyl, and X is hydrido;

7 0 R is 3-carboxyphenyl, B is 2-propyl, A is a bond, Y is 4-amidinobenzyl, and X is hydrido; 2 0

R is 3-aminophenyl, B is 2-propyl, A is a bond, Y is 4-amidino-3- fluorobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

R 2 is 3,5-diaminophenyl, B is (S)-2-butyl, A is a bond, Y 0 is 4- amidinobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y is 4-amidino-2- fluorobenzylbenzyl, and X is chloro;

2 0

R is 3,5-diaminophenyl, B is ethyl, A is a bond, Y is 4-amidinobenzyl, and

X is chloro;

2 0

R is 3,5-diaminophenyl, B is ethyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

2 0 R is 3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y is

4-amidinobenzyl, and X is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y is 4- amidino-2-fluorobenzylbenzyl, and X is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y is 4- amidinobenzyl, and X is chloro;

2 0

R is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 2,2,2-trifluoroethyl,

A is a bond, Y is 4-amidinobenzyl, and X is chloro; R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is (S)-2-butyl, A is a bond, Y is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y is 4-amidino-2-fluorobenzylbenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond, i is 4-amidinobenzyl, and X is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,

Y is 4-amidino-2-fluorobenzyl, and X is chloro; and

R 2 ιs 3,5-diaminophenyl, B is isopropyl, A is a bond, Y 0 is 4- amidinobenzylbenzyl, and X is hydrido.

45. Compound of Claim 22 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl, wherein

33 each ring carbon is optionally substituted with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substituted with oxo provided that no more than one ring carbon is substituted by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point

9 13 of attachment are optionally substitated with R or R , a ring carbon or

9 nitrogen adjacent to the R position and two atoms from the point of attachment

10 13 is optionally substitated with R , a ring carbon or nitrogen adjacent to the R position and two atoms from the point of attachment is optionally substituted

12 with R , a ring carbon or nitrogen three atoms from the point of attachment

and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent to the

12 33 R position is optionally substitated with R , and a ring carbon or nitrogen

11 33 four atoms from the point of attachment and adjacent to the R and R

34 positions is optionally substitated with R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboxy, carboxamido, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl , cycloalkylalkyl, heteroaryl , heterocyclyl , alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo, haloalkyl, and cyano;

33 34 R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, and cyano; 33 b

R is optionally Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1 , pa is an

7 7 7 integer selected from 0 through 3, and W is (R )NC(O) or N(R );

7 R is selected from the group consisting of hydrido, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, o 42 o

W -(CH(R ))_p wherein p is 0 or 1 and W is selected from the group

41 consisting of O, S, and N(R );

41 42

R and R are independently hydrido or alkyl; Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substitated by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substitated by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substituted by R , and any

10 12 11 carbon adjacent to both R and R is optionally substitated by R ;

Y is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substituted by Q , a carbon two or three g atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substituted by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substitated by R , another carbon adjacent to the point of

attachment of Q is optionally substituted by R , a carbon adjacent to Q is

16 h optionally substitated by R , and another carbon adjacent to Q is optionally

19 substitated by R ;

16 17 18 , _τ-.19 . R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

_^ 16 „ 19 . . „ _20 1 , _nΛm25, _xm23„24 . , ,

R or R is optionally NR R or and C(NR )NR R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

C(NR )NR R , with the proviso that no more than one of R and R is

23 hydroxy at the same time and with the further proviso that no more than one of R

24 and R is hydroxy at the same time;

20 21 23 24 25

R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, and hydroxy; g Q is selected from the group consisting of a bond, CH₂, and

CH₂CH₂.

46. Compound of Claim 45 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyπolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahy drothienyl, wherein each ring carbon is

33 optionally substitated with R , ring carbons and a nitrogen adjacent to the

9 carbon atom at the point of attachment are optionally substitated with R or

13 9 R , a ring carbon or nitrogen adjacent to the R position and two atoms from

10 the point of attachment is optionally substitated with R , and a ring carbon or

13 nitrogen adjacent to the R position and two atoms from the point of

12 attachment is optionally substitated with R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2333-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-l-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

R and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hy droxy ethyl, 2,2,2-trifluoro-l-hydroxyefhyl, methoxy carbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimeιhylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-( l-phenylethyl)amidocarbonyl, N-( 1 -methyl- 1 -phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy, cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy, cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy, 3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino, 5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl, 4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino, 4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl, chloroρyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy, 3,5-difluorophenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,

2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy, 3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy, 3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy, 3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy, 4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, 3-fluoro-5-trifluoromethylbenzyloxy,

4-fluoro-2-trifluoromethyIbenzyloxy, 4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy, 2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy, 4-fluorophenylamino, 2-fluoro-4-trifluoromethylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, 4-isoproρylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino, 1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino, phenylsulf onyl, 3-trifluoromethoxybenzyloxy, 4-trifiuoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy , 4-trifluoromethoxyphenoxy , 3-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy, 3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy, 4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy, 2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy, 3-pentafluoroethylphenoxy, 3-(l,l,2,2-tetrafluoroethoxy)phenoxy, and 3-trifluoromethylthiophenoxy;

33 R is selected from the group consisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,

2,23 3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,

N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro- 1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano, and Q ;

A is selected from the group consisting of a bond, NH, N(CH₃),

N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,

C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2- trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,

1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is Z°-Q; Z is selected from the group consisting of a bond, CH₂, CH₂CH₂, 0,

S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂;

Q is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyπolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and l,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to Z is

9 optionally substitated by R , the other carbon adjacent to the carbon at the point

13 9 of attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substitated by

R , a carbon adjacent to R and two atoms from the carbon at the point of

attachment is optionaHy suit d by R^K. and a„_y carbon adjacent ,„ both

„10 12 . . „ _u . _{J t}_ 1 1

R and R is optionally substituted by R ; Y is selected from the group consisting of:

, ^b _λ s „ 16 „ 17 _e 18 „ 19,

1-Q -4-Q _₂-R _3_R -5-R -6-R benzene,

„ _^ ^b _e s , „ 17 _Λ „ 18 19 . ,. 2-Q -5-Q -6-R -4-R -3-R pyridine,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-6-R¹⁸pyrazine,

3-Q^b-6-Q^S-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,

2-Q^b-5-Q^S-4-R¹⁷-6-R¹⁸pyrimidine, 5-Q^b-2-Q^S-4-R¹⁶-6-R¹⁹pyrimidine,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷thiophene,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹furan, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷furan,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹pyπole, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷pyπole, b s 19 b s 17

4-Q -2-Q -5-R imidazole, 2-Q -4-Q -5-R imidazole, T-. ^*ϊ £ ϊ-» 1 iZ -Q -5-Q -4-R isoxazole, 5-Q -3-Q -4-R isoxazole, b s 16 b s 19

2-Q -5-Q -4-R pyrazole, 4-Q -2-Q -5-R thiazole, and -1 rη

2-Q -5-Q -4-R thiazole;

16 17 1 R 1 Q

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,

N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3 ,3-pentafluoropropyl, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano;

RI⁶ or R « 19 i.s opti .ona „lly C(N_mR²⁵^ )N_mR²³ R.² wi -t,h_ t ,he provi •so th , at T R.¹⁶ ,

19 b

R , and Q are not simultaneously hydrido;

Q is C(NR )NR R or hydrido, with the proviso that no more than

23 24 one of R and R is hydroxy at the same time;

23 24 25

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, and hydroxy;

Q is selected from the group consisting of a bond, CH₂ and CH₂CH₂.

47. Compound of Claim 46 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, 1-pyπolidinyl, 1-piperidinyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 7-oxabicyclo[2.2. l]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piρerazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyπolidinyl, 2-pyπolidinyl, 3-pyπolidinyl, 2-dioxanyl, 4H-2-pyranyI, 4H-3-pyranyl, 4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl;

A is selected from the group consisting of a bond, CH₂, NHC(O),

CH₂CH₂, and CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro; R² is Z°-Q;

Z is selected from the group consisting of a bond, CH₂, 0, S, NH,

N(CH₃), OCH₂, and SCH₂;

Q is selected from the group consisting of

3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-benzylphenyl, 3-amino-5-(2-phenylethyl)phenyl,

3-amino-5-benzylaminophenyl, 3-amino-5-(2-phenylethylamino)phenyl,

3-amino-5-benzyloxyphenyl, 3-amino-5-(2-phenylethoxy)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-S(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-methyl-l-ρhenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-benzylamidosulfonyl)phenyl,

3-amino- (N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino- (N-ethylamidocarbonyl)phenyl,

3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-S(N-isobutylamidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl, 3-amino- (N-cyclobutylamidocarbonyl)phenyl,

3-amino-5-(N-cyclopentylamidocarbonyl)ρhenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, Samino-2-methylthiophenyl, 3 -aminophenyl , 3-amino-5-(4-trifluoromethylbenzylamino)phenyl , 3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl, 3-amino-5-carboxyphenyl, 3-chlorophenyl, 2-chloroρhenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminoρhenyl, 2-fluoroρhenyl, 3 -fluorophenyl, 2-hydroxyphenyl, 3-hydroxyρhenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminoρhenyl, 3-methoxycarbonylphenyl, 2-methylaminoρhenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;

Y is selected from the group consisting of:

, 1-Q _^ -4 _Λ-Q s _ _Λ2_R 16 - _3-R 17 _5 „_ „R18 _6 „-R 19, benzene, ι -• rη 1 1 Λ 2-Q -5-Q^S-6-R -4-R -3-R pyridine, > „ s „ 16 18 _Λ 19 . ,. 3-Q -6-Q -2-R -5-R -4-R pyridine,

„ b „ s , _ 16 „ „ 19 , . , , _Λ Jo _ _^s _ _^ 16 „ __ 17 , . ,

3-Q -5-Q -4-R -2-R thiophene, and 2-Q -5-Q -3-R -4-R thiophene;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano; τ.16 „19 . . „ _{^/ T},_25 _T 23 24 . , , . , 16

R or R is optionally C(NR )NR R with the proviso that R ,

19 h

R , and Q are not simultaneously hydrido;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q^b is C(NR²⁵)NR²³R²⁴ or hydrido;

23 24 25

R ^• , R , and R are independently hydrido or methyl;

Q^S is CH₂.

48. Compound of Claim 45 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl, wherein

33 each ring carbon is optionally substitated with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substitated with oxo provided that no more than one ring carbon is substitated by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon atom at the point

9 13 of attachment are optionally substituted with R or R , a ring carbon or

9 nitrogen adjacent to the R position and two atoms from the point of attachment

10 13 is optionally substitated with R , a ring carbon or nitrogen adjacent to the R position and two atoms from the point of attachment is optionally substitated

12 with R , a ring carbon or nitrogen three atoms from the point of attachment

and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent to the

12 33

R position is optionally substitated with R , and a ring carbon or nitrogen

11 33 four atoms from the point of attachment and adjacent to the R and R

34 positions is optionally substituted with R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano; R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido, carboxyalkyl, and cyano;

33 34

R and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, and cyano;

33 h R is optionally Q ;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1 , pa is an

7 7 integer selected from 0 through 3, and W is N(R );

7 R is hydrido or alkyl;

15 R is selected from the group consisting of hydrido, halo, alkyl, and haloalkyl;

X° is selected from the group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo;

R² is Z°-Q; Z is a bond;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o . 9 ring to Z is optionally substitated by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substitated by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

optionally substituted by R , a carbon adjacent to R and two atoms from the 12 carbon at the point of attachment is optionally substitated by R , and any

10 12 11 carbon adjacent to both R and R is optionally substitated by R ;

Y is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbon g of said phenyl or said heteroaryl is substitated by Q , a carbon two or three s atoms from the point of attachment of Q to said phenyl or said heteroaryl is b s substitated by Q , a carbon adjacent to the point of attachment of Q is

17 optionally substitated by R , another carbon adjacent to the point of

attachment of Q is optionally substitated by R , a carbon adjacent to Q is

16 b optionally substitated by R , and another carbon adjacent to Q is optionally

19 substitated by R ;

„ 16 17 18 19 . ₃ , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

_« 16 „19 . . „ _TT 20 21 _{^/ τπ}25_N 23 24 . , , R or R is optionally NR R or C(NR )NR R , with the

16 19 b proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, and

25 23 24 C(NR )NR R ;

20 21 23 24 25 R , R , R , R , and R are independently hydrido or alkyl;

Q^s is CH₂.

49. Compound of Claim 48 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl, 2-mo holinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-ρiperidinyl, 1 -pyπolidinyl, 2-pyπolidinyl, 3-pyπolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahy dropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each

33 ring carbon is optionally substituted with R , ring carbons and a nitrogen adjacent to the carbon atom at the point of attachment are optionally substituted

9 13 9 with R or R , a ring carbon or nitrogen adjacent to the R position and two

10 atoms from the point of attachment are optionally substitated with R , and a

13 ring carbon or nitrogen atom adjacent to the R position and two atoms from

12 the point of attachment is optionally substitated with R ;

9 11 13

R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,

N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,

1 -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;

R and R are independently selected from the group consisting of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,

N-(3-fiuorobenzyI)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-(l-phenylethyl)amidocarbonyl, N-(l-methyl-l-ρhenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,

N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino, dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro, chloro, bromo, and cyano;

33 R is selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, cyano, and Q^b;

A is selected from the group consisting of a bond, NH, N(CH₃), CH₂,

CH₃CH, CH₂CH₂, and CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro;

R is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyπolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to the 1,4-quinone ring is optionally substituted by

9

R , the other carbon adjacent to the carbon at the point of attachment is

13 9 optionally substitated by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is optionally substitated by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment is

12 10 12 optionally substituted by R , and any carbon adjacent to both R and R is

optionally substituted by R ; Y is selected from the group consisting of:

, _^ ^b _{Λ ^}s _Λ 16 ,_ „17 _e „18 , 19,

1-Q -4-Q -2-R -3-R -5-R -6-R benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine, 2-Q^b-5-Q^S-3-R¹⁶-4-R¹⁷thiophene,

3-Q^b-6-Q^S-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹thiophene,

3-Q^b-5-Q^S-4-R¹⁶-2-R¹⁹furan, 2-Q^b-5-Q^S-3-R¹⁶-4-R^1?furan,

3-Q -5-Q^S-4-R -2-R pyπole, 2-Q -5-Q^S-3-R -4-R pyπole, b s 19 b s 17

4-Q -2-Q -5-R thiazole, and 2-Q -5-Q -4-R thiazole;

16 17 18 19

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1 -aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifIuoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano; b 20 21 25 23 24

Q is NR R or C(NR )NR R ;

20 21 23 24 25 R , R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl; Q^S is CH₂.

50. Compound of Claim 49 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 1-pyπolidinyl and 1-piperidinyl;

A is selected from the group consisting of a bond, CH₂, CH₂CH₂ and

CH₂CH₂CH₂; X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro; R is selected from the group consisting of 3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl,

3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)ρhenyl,

3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-( 1 -phenyl ethyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl,

3 -amino-5-(N-benzylamidosulf onyl)phenyl ,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,

3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl,

3-amino-5-(N-propylamidocarbonyl)phenyl,

3-amino-5-(N-isobutylamidocarbonyl)phenyl,

3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,

3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,

3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyρhenyl, 3-carboxy-5-aminophenyl, 3-carboxy-5-hydroχyphenyl, 3-carboxymethyl-5-aminophenyl,

3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3 -fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyρhenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl,

2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylρhenyl, phenyl, 3-trifluoroacetamidoρhenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; ϊ is selected from the group consisting of: l-Q^b-4-Q^S-2-R¹⁶-3-R^1?-5-R¹⁸-6-R¹⁹benzene,

2-Q^b-5-Q^S-6-R¹⁷-4-R¹⁸-3-R¹⁹pyridine,

„ _^b „ _Λ 16 18 , 19 . ,. 3-Q -6-Q -2-R -5-R -4-R pyridine,

3-Q -5-Q^S-4-R -2-R thiophene, and 2-Q -5-Q^S-3-R -4-R thiophene;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; b 25 23 24

Q is C(NR )NR R ;

23 24 25

R , R , and R are independently hydrido or methyl;

Q^s is CH₂.

51. Compound of Claim 50 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, and 1-piperidinyl; A is selected from the group consisting of a bond, CH₂, CH CH₂ and

CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, amino, amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro; R is selected from the group consisting of

3-amidocarbonyl- aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl, 3-amino- (N-(l-methyl-l-phenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-benzylamidosulf onyl)phenyl ,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-propylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino- (N-(2-butyl)amidocarbonyl)phenyl, 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 3-aminophenyl, 3-carboxy-5-aminophenyl, 3-chlorophenyl, 3 ,5-diaminophenyl,

3-dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylρhenyl, phenyl, 3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; i is selected from the group consisting of 5-amidino-2-thienylmethyl, 4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amdinobenzyl.

52. Compound of Claim 45 where said compound is selected from the group of the Formula:

or a pharmaceutically acceptable salt thereof , wherein B, A, R ,X , andY are selected to form a compound selected from the group consisting of; 7 0

R is 3-aminophenyl, B is cyclopropyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

R 2 is 3-aminophenyl, B is cyclobutyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X° is chloro; R 2 is 3-aminophenyl, B is cyclobutyl, A is a bond, Y 0 is 4-amidinobenzyl, and X° is chloro;

7 0

R is 3-aminophenyl, B is cyclopropyl, A is a bond, Y is 4~amidino-2- fluorobenzyl, and X° is chloro;

2 0

R is 3-aminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

7 0

R is 3-aminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3- fluorobenzyl, and X° is chloro;

7 0

R is 3-aminophenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

7 o R is 5-amino-2-thienyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

7 o

R is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y is 4-amidinobenzyl, and X° is chloro;

7 0

R is 3-aminophenyl, B is 2-(2R)-bicyclo[2.2.1]-heptyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R 2 is 3-aminophenyl, B is cyclopentyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X° is chloro;

7 0

R is 3-aminophenyl, B is cyclohexyl, A is CH CH₂, Y is 4- amidinobenzyl, and X° is hydrido;

7 0 R is 3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y is 4-amidinobenzyl, and X° is chloro; 7 0

R is 3-aminophenyl, B is 1-piperidinyl, A is CH₂CH₂, Y is 4- amidinobenzyl, and X° is chloro;

7 0

R is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH₂CH₂CH₂,Y is 4- amidinobenzyl, and X° is chloro;

7 0 R is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

7 o

R is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

7 0

R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

R 7 is 2-amino-6-carboxy-4-pyridyl, B is cyclobutyl, A is a bond, Y o is

4-amidinobenzyl, and X° is hydrido;

7 0

R is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

7 0 R is 3-amino-Scarboxyphenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

7 0

R is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

R 7 is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y 0 is 4-amidino-2- fluorobenzyl, and X° is chloro;

7 0

R is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2- fluorobenzyl, and X° is chloro;

7 0

R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

7 0 R is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3- fluorobenzyl, and X° is chloro; 7 0

R is 3,5-diaminophenyl, B is cyclopentyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

R 2 is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y 0 is 4- amidinobenzyl, and X° is chloro;

2 0 R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidino-2-fluorobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y is 4- amidino-2-fluorobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidinobenzyl, and X° is hydrido;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y is 4- amidino-3-fluorobenzyl, and X° is chloro;

2 0

R is 3-carboxy-5-aminophenyl, B is cyclopentyl, A is a bond, Y is 4- amidinobenzyl, and X° is chloro;

RR is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro; R is 3-amino-5-(N-benzylamidocarbonyl)ρhenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro; R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro; 2

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fiuorobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)ρhenyl, B is cyclopropyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro;

2 R is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclopropyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

2

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-ρhenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-2-fluorobenzyl, and X° is chloro;

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro;

R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclopropyl, A is a bond, Y is amidino-2-fluorobenzyl, and X° is chloro; R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidinobenzyl, and X° is hydrido; R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is cyclobutyl, A is a bond, Y is 4-amidino-3-fluorobenzyl, and X° is chloro; and

2 R is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl,

B is cyclopentyl, A is a bond, Y is 4-amidinobenzyl, and X° is chloro.

53. Compound of Claim 22 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl

32 ring to A is optionally substitated by R , the other carbon adjacent to the

carbon at the point of attachment is optionally substituted by R , a carbon

32 adjacent to R and two atoms from the carbon at the point of attachment is

• „ , • , , _r.33 , „36 , _c optionally substituted by R , a carbon adjacent to R and two atoms from the

35 carbon at the point of attachment is optionally substituted by R , and any

33 35 34 carbon adjacent to both R and R is optionally substitated by R ;

32 33 34 35 36

R ,R , R , R , andR are independently selected from the group consisting of hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl, alkylamino, carboalkoxy, carboxy, carboxamido, cyano, and Q ;

B is optionally selected from the group consisting of hydrido, trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member of group B is optionally substitated at any carbon up to and including 6 atoms from the point of attachment of B to A

32 33 34 35 36 with one or more of the group consisting of R , R , R , R , and R ;

B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,

33 wherein each ring carbon is optionally substitated with R , a ring carbon other than the ring carbon at the point of attachment of B to A is optionally substitated with oxo provided that no more than one ring carbon is substitated by oxo at the same time, ring carbons and a nitrogen adjacent to the carbon

9 13 atom at the point of attachment are optionally substitated with R or R , a ring

9 carbon or nitrogen adjacent to the R position and two atoms from the point of

attachment is optionally substitated with R , a ring carbon or nitrogen adjacent

13 to the R position and two atoms from the point of attachment is optionally

12 substituted with R , a ring carbon or nitrogen three atoms from the point of

attachment and adjacent to the R position is optionally substituted with R , a ring carbon or nitrogen three atoms from the point of attachment and adjacent

12 33 to the R position is optionally substitated with R , and a πng carbon or

nitrogen four atoms from the point of attachment and adjacent to the R and

33 34

R positions is optionally substituted with R ;

9 10 1 1 12 13

R , R , R , R , and R are independently selected from the group consisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy, cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy ,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino, heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, and cyano;

15 7

A is a bond or (CH(R ))_pa-(W )_rr wherein π is 0 or 1 , pa is an

7 integer selected from 0 through 3 , and W is selected from the group

consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R^?);

7 R is selected from the group consisting of hydπdo, hydroxy and alkyl;

15 R is selected from the group consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; X is selected from the group consisting of hydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z°-Q; o . 41 42

Z is selected from the group consisting of a bond, (CR R )_q

41 o 42 wherein q is 1 or 2, and (CH(R ))_«-W -(CH(R ))„ wherein g and p are integers independently selected from 0 through 3 and W is selected from the

41 41 group consisting of O, S, C(O), S(O), N(R ), and ON(R );

Z° is optionally (CH(R⁴¹))_e-W²²-(CH(R⁴²))_h wherein e and h are

independently 0 or 1 and Vv is selected from the group consisting of

41 42 CR =CR , 1,2-cycloproρyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 13-cyclohexyl,

1,2-cyclopentyl, 1 -cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl, 2,6-morρholinyI, 3,4-morpholinyl, 3,5-morphoIinyl, 1,2-ρiperazinyl, 13-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, l,2-ρyπolidinyl,13-pyrrolidinyl, 23-pyπolidinyl, 2,4-pyπolidinyl, 2,5-pyπolidinyl, 3,4-pyπolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, wherein Z is directly bonded to the 1,4-quinone ring and W^ is optionally substitated with one or more

9 10 11 12 13 substituents selected from the group consisting of R , R , R , R , and R ;

41 42

R and R are independently selected from the group consisting of hydrido, hydroxy, alkyl, and amino; Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl o 9 ring to Z is optionally substituted by R , the other carbon adjacent to the

13 carbon at the point of attachment is optionally substitated by R , a carbon

9 adjacent to R and two atoms from the carbon at the point of attachment is

10 13 optionally substituted by R , a carbon adjacent to R and two atoms from the

12 carbon at the point of attachment is optionally substitated by R , and any

10 12 11 carbon adjacent to both R and R is optionally substitated by R , with the proviso that Q is other than a phenyl when Z is a bond;

Q is optionally hydrido with the proviso that Z is selected from other than a bond;

4a 4a

K is CHR wherein R is selected from the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E is selected from the group consisting of a bond, C(O)N(H),

(H)NC(O), (R^?)NS(O)₂, and S(O)₂N(R^?);

Y^ is Q V; 37 38 Q is (CR R )b wherein b is an integer selected from 1 through 4,

37 R is selected from the group consisting of hydrido, alkyl, and haloalkyl, and

38 R is selected from the group consisting of hydrido, alkyl, haloalkyl, aroyl, and heteroaroyl with the proviso that there is at least one aroyl or heteroaroyl substituent, with the further proviso that no more than one aroyl or heteroaroyl

37 38 is bonded to (CR R ^ at the same time, with the still further proviso that said aroyl and said heteroaroyl are optionally substituted with one or more

, • • ._τ, 16 _nV7 „18 19 substituents selected from the group consisting oi R , R , R , and R , with another further proviso that said aroyl and said heteroaroyl are bonded to the CR R that is directly bonded to E , with still another further proviso

37 38 that no more than one alkyl or one haloalkyl is bonded to a CR R at the same time, and with the additional proviso that said alkyl and haloalkyl are bonded to a carbon other than the one bonding said aroyl or said heteroaroyl;

Λ g 1 *7 i Q 1 Q

R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R or R is optionally selected from the group consisting of

NR R ,N(R )C(NR )N(R )(R ), and C(NR )NR R , with the

proviso that R , R , and Q are not simultaneously hydrido; b 20 21

Q is selected from the group consisting of NR R , hydrido, r ^sr ' OA *C Υ OA

N(R )C(NR )N(R )(R ), and C(NR )NR R , with the proviso that

20 21 no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time and with the 23 24 further proviso that no more than one of R and R is selected from the group consisting of hydroxy, amino, alkylamino, and dialkylamino at the same time;

„20 21 23 24 25 26 . _{Λ J} , ,

R , R , R , R , R , and R are independently selected from the group consisting of hydrido, alkyl, hydroxy, amino, alkylamino and dialkylamino.

54. Compound of Claim 53 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyπolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or

32 heteroaryl ring to A is optionally substituted by R , the other carbon adjacent

36 to the carbon at the point of attachment is optionally substitated by R , a

32 carbon adjacent to R and two atoms from the carbon at the point of

Q ^f attachment is optionally substituted by R , a carbon adjacent to R and two atoms from the carbon at the point of attachment is optionally substitated by R , and any carbon adjacent to both R and R is optionally substitated by

34

R

32 33 34 35 36

R , R , R , R , and R are independently selected from the group consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q ; B is optionally selected from the group consisting of hydrido, ethyl,

2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, l-methyl-2-pentenyl, l-methyl-3-pentenyl, l-methyl-2-pentynyl, l-methyl-3-pentynyl, 3-hexyl, l-ethyl-2-butenyl, 1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyI, 5-heptenyl, 2-heptynyI, 3-heptynyl, 4-heptynyl, 5-heρtynyl, 2-heptyl, l-methyl-2-hexenyl, l-methyl-3-hexenyl, l-methyl-4-hexenyl, l-methyl-2-hexynyl, l-methyl-3-hexynyl, l-methyl-4-hexynyl, 3-heptyl, l-ethyl-2-pentenyl, l-ethyl-3-pentenyl, l-ethyl-2-pentynyl, l-ethyl-3-pentynyl, 2,2,2-trifluoroethyl, 2,2-difluoropropyl, 4-trifluoromethyl-5,5, trifluoropentyl, 4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and 33,3-trifluoropropyl, wherein each member of group B is optionally substituted at any carbon up to and including 5 atoms from the point of attachment of B to A with one or more of the group

„ 32 33 34 35 _, 36 consisting of R , R , R , R , and R ;

B is optionally selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-ρiρerazinyl, 2-ρiperazinyl, 1-piperidinyl, 2-ρiperidinyl, 3-piρeridinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyπolidinyl, 3-pyπolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and

3-tetrahydrothienyl, wherein each ring carbon is optionally substitated with

33 R , ring carbons and a nitrogen adjacent to the carbon atom at the point of

9 13 attachment are optionally substituted with R or R , a πng carbon or nitrogen 9 adjacent to the R position and two atoms from the point of attachment is

optionally substitated with R , and a ring carbon or nitrogen adjacent to the

13 R position and two atoms from the point of attachment is optionally

12 substituted with R ;

9 11 13 R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl, 1 -hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, and cyano;

10 12

R and R are independently selected from the group consisting of hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl, N-(2-trifluoromethylbenzyl)amidocarbonyl, N-( l-phenylethyl)amidocarbonyl, N-( 1-methyl- l-phenylethyl)amidocarbonyl, N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl, N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl, N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl, N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl, N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hy droxy ethyl, carboxy, carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyI, trifluoroacetamido, aminomethyl, N-methylamino, dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, methanesulfonamido, methoxy carbonyl, fluoro, chloro, bromo, and cyano;

A is selected from the group consisting of a bond, NH, N(CH₃), CH₂,

CH₃CH, CH₂CH₂, and CH₂CH₂CH₂; X° is selected from the group consisting of hydrido, hydroxy, hydroxymethyl, amino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy, methylthio, trifluoromethoxy, fluoro, and chloro;

2 R is selected from the group consisting of phenyl, 2-thienyl, 2-furyl, 2- pyπolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at the point of attachment of said phenyl or heteroaryl ring to the 1,4-quinone ring is optionally substitated by

9 R , the other carbon adjacent to the carbon at the point of attachment is

13 9 optionally substituted by R , a carbon adjacent to R and two atoms from the

carbon at the point of attachment is optionally substitated by R , a carbon

13 adjacent to R and two atoms from the carbon at the point of attachment is

• „ , ■ _ι , „12 , , ,. , , _n10 12 . optionally substituted by R , and any carbon adjacent to both R and R is

11 optionally substituted by R ;

Y^AT is Q^b-Q^S s Q is selected from the group consisting of:

37 37 38

C[R (benzoyl)(CR R )_b],

37 37 38

C[R (2-pyridylcarbonyl)(CR R )_b],

C[R³⁷(3-pyridylcarbonyl)(CR³⁷R³⁸)_b],

C[R^3?(4-pyridylcarbonyl)(CR³⁷R³⁸)_b],

37 37 38 C[R (2-thienylcarbonyiχCR R )_b], n O

C[R (3-thienylcarbonyl)(CR R )_b],

C[R³⁷(2-thiazolylcarbonyl)(CR³⁷R³⁸)_b],

37 37 38

C[R (4-thiazolylcarbonyl)(CR R ) ], and 37 37 38

C[R (5-thiazoιylcarbonyl)( (CR R )_b], wherein b is an integer selected

37 38 from 1 through 3, R and R are independently selected from the group consisting of hydrido, alkyl, and haloalkyl, with the proviso that said benzoyl and the heteroaroyls are optionally substitated with one or more substituents

_Λ , • • _{^ τ},16 „17 „18 , 19 . , , selected Irom the group consisting of R , R , R , and R with the proviso

17 18 that R and R are optionally substituted at a carbon selected from other than the meta and para carbons relative to the carbonyl of the benzoyl or heteroaroyl, with the further proviso that said benzoyl or said heteroaroyl are bonded to the carbon directly bonded to amide nitrogen of the l-(amidocarbonymethylene) group, and with the still further proviso that is no more than one alkyl or one

37 38 haloalkyl is bonded to a CR R at the same time;

„16 17 18 19 . , , , ,

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano;

Q is C(NR )NR R or N(R )C(NR )N(R )(R );

23 24 25 26

R , R , R , and R are independently selected from the group consisting of hydrido, methyl, and ethyl.

55. Compound of Claim 54 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl,

3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4-dichloroρhenyl, 2-fluorophenyl, 3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hy droxy phenyl, 3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazoyl, 2-pyridyl, 3-pyridyl, 5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, and

3-trifluoromethyl-2-pyridyl ;

B is optionally selected from the group consisting of hydrido, ethyl,

2-proρenyl, 2-proρynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl,

2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl,

3-hydroxypropyl, l-methoxy-2-propyl, 2-methoxy ethyl, 2-methyl-2-butyl,

3-methyl-2-butyl, 2-dimethylaminoρropyl, 2-cyanoethyl, 6-hydroxyhexyl,

2-hydroxy ethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl,

2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl,

3-aminopropyl, 2-hexyl, and 4-aminobutyl;

B is optionally selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 1-pyπolidinyl and

1-piperidinyl;

A is selected from the group consisting of a bond, CH₂, CH3CH,

CH₂CH₂, and CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, hydroxymethyl, amino, aminomethyl, cyano, methyl, trifluoromethyl, fluoro, and chloro;

R is selected from the group consisting of 3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl, 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-( 1 -phenylethyl)amidocarbonyl)phenyl , 3-anιino-5-(N-(l-methyl-l-ρhenylethyl)amidocarbonyl)phenyl, 3-amino-5-(N-benzylamidosulfonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl, 3-amino-5-(N-isopropylamidocarbonyl)phenyl, 3-amino-5-(N-proρylamidocarbonyl)phenyl, 3-amino-5-(N-isobutylamidocarbonyl)phenyl, 3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl, 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, 3-amino-5-(N-cycloρentylamidocarbonyl)phenyl, 3-amino-5-(N-cyclohexylamidocarbonyl)ρhenyl,

5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl, 3 -carboxy-5-hy droxy phenyl, 3-carboxymethyl-5-aminophenyl, 3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl, ,5-diaminophenyl, 3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyρhenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylρhenyl, phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y^AT is Q^b-Q^S;

Q is selected from the group consisting of:

[CH(benzoyl)](CH₂)_b, [CH(2-pyridylcarbonyl)](CH₂)_b,

[CH(3-pyridylcarbonyl)](CH₂)_b, [CH(4-pyridylcarbonyl)](CH₂)_b,

[CH(2-thienylcarbonyl)](CH₂)_b,[CH(3-thienylcarbonyl)](CH₂)_b,

[CH(2-thiazolylcarbonyl)](CH₂)_b, [CH(4-thiazolylcarbonyl)](CH₂)_b,

and [CH(5-thiazolylcarbonyl)](CH₂) , wherein b is an integer selected from 1 through 3, with the proviso that said benzoyl and said heteroaroyls are optionally substitated with one or more substituents selected from the group

1 17 1 δ 10 1 *7 1 & consisting of R , R , R , and R with the proviso that R and R are optionally substitated at a carbon selected from other than the meta and para carbons relative to the carbonyl of the benzoyl or the heteroaroyl, and that said benzoyl or said heteroaroyl are bonded to the carbon directly bonded to amide nitrogen of the l-(amidocarbonymethylene) group;

R and R are independently selected from the group consisting of hydrido, amidino, amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;

17 18

R and R are independently selected from the group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano;

, ^ ^X OA

Q is N(R )C(NR )N(R )(R );

23 24 25 26 R , R , R , and R are independently hydrido or methyl.

56. Compound of Claim 55 or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl, 4-chlorophenyl,

3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl, phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and 3-trifluoromethyl-2-pyridyl;

B is optionally selected from the group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl,

2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl, l-methoxy-2-propyl, 2-methoxy ethyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl,

2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl;

B is optionally selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, and 1-piperidinyl; A is selected from the group consisting of a bond, CH₂, CH₂CH₂ and

CH₂CH₂CH₂;

X° is selected from the group consisting of hydrido, hydroxy, hydroxymethyl, amino, aminomethyl, cyano, methyl, trifluoromethyl, and fluoro;

2

R is selected from the group consisting of

3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,

3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-phenylethyl)amidocarbonyl)phenyl,

3-amino-5-(N-(l-methyl-l-phenylethyl)amidocarbonyl)ρhenyl,

3-amino-5-(N-benzylamidosulfonyl)phenyl,

3-amino- (N-(2-chlorobenzyl)amidosulfonyl)ρhenyl, 3-amino-5-(N-ethylamidocarbonyl)phenyl ,

3-amino-5-(N-isopropylamidocarbonyl)phenyl,

3-amino-5-(N-propylamidocarbonyl)ρhenyl,

3-amino-5-(N-isobutylamidocarbonyl)phenyl,

3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl, 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,

3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,

3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 3-aminophenyl,

3-carboxy-5-aminophenyl, 3-chlorophenyl, 3,5-diaminophenyl,

3-dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methylaminophenyl, 2-methylphenyl, 3-methylρhenyl, phenyl,

3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; i is selected from the group consisting of 5-guanidino-l-oxo-l-(2- thiazolyl)-2-pentyl, 5-guanidino-l-oxo-l-(4-thiazolyl)-2-penιyl, 5-guanidino-l- oxo- 1 -(5-thiazolyl)-2-pentyl , 5- guani dino- 1 -oxo- 1 -(4-amino-2-thiazolyl)-2- pentyl, and 5-guanidino-l-oxo-l-phenyl-2-pentyl.

57. A compound as recited in Claim 53 where said compound is selected from the group of the Formula:

or a pharmaceutically acceptable salt thereof, wherein B, A, R , X°, and Y are selected to form a compound selected from the group consisting of;

2 AT

R is 3-aminophenyl, B is phenyl, A is CH₂CH₂,Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 AT

R is 3,5-diaminoρhenyl, B is phenyl, A is CH₂CH₂, Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 AT

R is 3-carboxy-5-aminophenyl, B is phenyl, A is CH₂CH₂,Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is phenyl, A is

AT o

CH CH₂,Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X is chloro;

7 AT

R is 3,5-diaminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; AT

R is 3-carboxy-5-aminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino- 1 -oxo- l-(2-thiazolyl)-2-pentyl, and X° is chloro;

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is

AT o single bond, Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X is chloro; AT

R is 3,5-diaminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; AT

R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro; R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is

ΔT single bond, Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is chloro;

2 AT

R is 3-aminophenyl, B is phenyl, A is CH₂CH₂, Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-ρentyl, and X° is hydrido;

2 AT R is 3,5-diaminophenyl, B is phenyl, A is CH₂CH₂, Y is 5-guanidino-l- oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2 AT

R is 3-carboxy-5-aminophenyl, B is phenyl, A is CH₂CH₂,Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

2 R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is phenyl, A is

AT CH₂CH₂,Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-ρentyl, and X° is hydrido;

2 AT

R is 3,5-diaminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)~2-pentyl, and X° is hydrido;

7 AT

R is 3-carboxy-5-aminophenyl, B is isopropyl, A is single bond, Y is 5- guanidino- 1 -oxo- l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

R is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is

AT o single bond, Y is 5-guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X is hydrido; AT

R is 3,5-diaminoρhenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido;

9 AT R is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is single bond, Y is 5- guanidino-l-oxo-l-(2-thiazolyl)-2-pentyl, and X° is hydrido; and

R is 3-amino-5-(N-benzylamidocarbonyl)ρhenyl, B is cyclobutyl, A is single bond, Y is 5-guanidino- 1-oxo- 1 -(2-thiazolyl)-2-pentyl, and X° is hydrido.

58. A composition for inhibiting thrombotic conditions in blood comprising a compound of Claim 21 and a pharmaceutically acceptable carrier.

59. A method for inhibiting thrombotic conditions in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 58.

60. A method for inhibiting formation of blood platelet aggregates in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 58.

61. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of a composition of Claim 58.

62. A method for treating or preventing venuous thromboembolism and pulmonary embolism in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

63. A method for tieating or preventing deep vein thrombosis in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

64. A method for treating or preventing cardiogenic thromboembolism in a mammal comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

65. A method for treating or preventing thromboembolic stroke in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

66. A method for treating or preventing thrombosis associated with cancer and cancer chemotherapy in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

67. A method for treating or preventing unstable angina in humans and other mammals comprising administering to the mammal a therapeutically effective amount of a composition of Claim 58.

68. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of a compound of Claim 21 with a therapeutically effective amount of fibrinogen receptor antagonist.

69. The use of a compound of Claim 21, or a pharmaceutically acceptable salt thereof, in the manufacture of medicament for inhibiting thrombus formation, treating thrombus formation, or preventing thrombus formation in a mammal.