JPWO2022245759A5 - - Google Patents

Description

Preparation of compound 1293:
To a mixture of intermediate 23 (120.0 mg, 58.50 μmol, 1.00 equiv) and FITC (34.08 mg, 87.51 μmol, 1.50 equiv) in DMF (2 mL) was added DIEA (27.7 mg, 30.59 μL, 175.5 μmol, 3.00 equiv) at 25° C. The mixture was stirred at 25° C. for 2 h. After completion monitored by LC-MS, the mixture was acidified to pH=5 with 1M HCl and then directly purified by preparative HPLC (A: 0.075% TFA/H ₂ O, B: MeCN) followed by lyophilization to give compound 1293 (33.8 mg, 91.4% purity, 23.7% yield) as a yellow solid. LCMS: RT = 2.02 min, MS calculated: M _average = 2440.69, observed masses: [M+Na+H] ²⁺ = 1232.00, [M+2H] ²⁺ = 1221.60, [M+3H] ³⁺ = 814.30.
The present application also includes the following aspects.
[Aspect 1]
A compound having the structure of formula R-I,
LG-RG-L ^RM -MOI
(R-I)
or a salt thereof, wherein
LG is a group that comprises a target binding moiety that binds to a targeting agent;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' are optionally joined to form a ring;
LLG3 is ^an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
LRG1 is ^-C (O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" are optionally joined to form a ring;
L ^RM is a linker;
The MOI is the moiety of interest, a compound or a salt thereof.
[Aspect 2]
RG is or includes a reactive group having the formula:
The compound according to embodiment 1, wherein ARYL is a substituted or unsubstituted para-phenylene ring.
[Aspect 3]
ARYL is,
The compound according to aspect 2, having the structure: wherein R ^s is independently selected at each occurrence from halogen, —NO ₂ , —F, -L-R', —C(O)-L-R', —S(O)-L-R', —S(O) ₂ -L-R', and —P(O)(-L-R') ₂ , and R' is H or C ₁ -C ₆ alkyl.
[Aspect 4]
4. The compound according to any one of the preceding claims, wherein the reactive group is or comprises one of the following formulae:
[Aspect 5]
RG is or includes a reactive group having the formula:
The compound according to embodiment 1, wherein ARYL is a substituted or unsubstituted para-phenylene ring.
[Aspect 6]
ARYL is,
The compound according to aspect 5, having the structure: wherein R ^s is independently selected at each occurrence from halogen, —NO ₂ , —F, -L-R', —C(O)-L-R', —S(O)-L-R', —S(O) ₂ -L-R', and —P(O)(-L-R') ₂ , and R' is H or C ₁ -C ₆ alkyl.
[Aspect 7]
7. The compound according to any one of the preceding claims, wherein the reactive group is or comprises one of the following formulae:
[Aspect 8]
LG is R ^LG -LLG ^,
RLG is ^​
, R ^c -(Xaa)z-, a nucleic acid moiety, or a small molecule moiety;
each Xaa is independently a residue of an amino acid or amino acid analog;
t is 0 to 50;
z is 1 to 50;
each R ^c is independently -L ^a -R';
each L ^a is independently a covalent bond or an optionally substituted divalent group selected from C ₁ -C ₂₀ aliphatic or C ₁ -C ₂₀ heteroaliphatic having 1 to 5 heteroatoms, wherein one or more methylene units of said group are optionally and independently replaced with C(R') ₂ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ₂ -, -S(O) ₂ N(R')-, -C(O)S-, or -C(O)O-;
each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently selected from a C 3-20 alicyclic _ring , a C _6-20 aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms;
L ^LG is -L ^LG1 -, -L ^LG1 -L ^LG2 -, -L ^LG1 -L ^LG2 -L ^LG3 -, or -L ^LG1 -L ^LG2 -L ^LG3 -L ^LG4 -,
Each of L ^LG1 , L ^LG2 , L ^LG3 , and L ^LG4 is independently a covalent bond, or a divalent optionally substituted linear or branched C 1-100 group comprising one or more aliphatic moieties, aryl moieties, heteroaliphatic moieties each independently having 1 to 20 heteroatoms, heteroaromatic moieties each independently having 1 to 20 heteroatoms, or any combination of any one or more of such moieties, wherein one or more methylene units of said group are optionally and independently selected from C _1-6 alkylene, C _1-6 alkenylene, a divalent C 1-6 heteroaliphatic group having 1 to 5 heteroatoms _{, -C≡C-} , -Cy-, -C(R') ₂ -, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R') ₂ N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ₂ -, -S(O) ₂ is replaced by N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, an amino acid residue or -[(-O-C(R') ₂ -C(R') ₂ -) _n ]- (wherein n is 1 to 20);
each R' is independently -R, -C(O)R, -CO ₂ R, or -SO ₂ R;
each R is independently -H or an optionally substituted group selected from C1-30 _aliphatic , C1-30 heteroaliphatic having 1-10 heteroatoms , C6-30 aryl, C6-30 arylaliphatic, _C6-30 arylheteroaliphatic _having 1-10 heteroatoms, _5-30 membered heteroaryl having 1-10 heteroatoms, and _3-30 membered heterocyclyl having 1-10 heteroatoms;
two R groups, optionally and independently, taken together form a covalent bond, or
two or more R groups on the same atom optionally and independently combine with said atom to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said atom, 0-10 heteroatoms; or
The compound according to aspect 1, wherein two or more R groups on two or more atoms are optionally and independently taken together with their intervening atoms to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having, in addition to said intervening atoms, 0-10 heteroatoms.
[Aspect 9]
2. The compound of aspect 1, wherein LG is or comprises a target binding moiety that binds to a targeting agent, said targeting agent being an antibody agent.
[Aspect 10]
2. The compound according to aspect 1, wherein LG is or comprises a target binding moiety that binds to an Fc region, and/or R ^LG is or comprises DCAWXLGELVWCT (SEQ ID NO: 2), wherein the two cysteine residues optionally form a disulfide bond, and X is an amino acid residue.
[Aspect 11]
The following conditions
(a) the moiety of interest is or comprises a therapeutic agent;
(b) the moiety of interest is or comprises a moiety capable of binding to a protein, a nucleic acid, or a cell; and/or
(c) the moiety of interest is or comprises a reactive moiety suitable for a bioorthogonal reaction.
[Aspect 12]
The compound according to aspect 1, wherein LG is or comprises a target binding moiety having a structure of any of Formulas A-1 to A-50 as shown herein.
[Aspect 13]
The compound of aspect 1, wherein the MOI is or comprises a therapeutic drug moiety and/or the MOI is or comprises an antibody drug.
[Aspect 14]
Compounds according to aspect 1, wherein L ^RM contains one or more -[(CH ₂ ) _n -O] _m -, where each n is independently 1-20, and m is 1-100.
[Aspect 15]
In formula (R-I),
the targeting agent is an antibody comprising an IgG heavy chain comprising K246 or K248;
2. The compound of aspect 1, wherein the target binding moiety is configured to bind to the antibody in a manner that brings the reactive group into proximity with K246 or K248 of the IgG heavy chain to allow reaction between K246 or K248 and the reactive group, resulting in binding of a moiety comprising an LRM-MOI to K246 or ^K248 and removal of the group containing the target binding moiety from the compound.
[Aspect 16]
A drug having the structure of P-I,
P-L ^PM -MOI
(P-I)
or a salt thereof, comprising the steps of:
P is a targeting drug moiety;
L ^PM is a linker,
MOI is the moiety of interest
1) a targeting agent and a reaction partner having the structure of formula R-I;
LG-RG-L ^RM -MOI
(R-I)
or a salt thereof, wherein
LG is a group that comprises a target binding moiety that binds to a targeting agent;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' are optionally joined to form a ring;
LLG3 is ^an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
LRG1 is ^-C (O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" are optionally joined to form a ring;
L ^RM is a linker;
MOI is a portion of interest;
2) forming a drug having the structure P-I; or
A method for preparing a drug having the structure of P-II, comprising the steps of:
P-N-L ^PM -MOI
(P-II)
During the ceremony,
P-N is a protein drug moiety containing a lysine residue;
L ^PM is a linker,
MOI is the moiety of interest
The method further comprising:
P-N and a reaction partner having the structure of formula R-I,
LG-RG-L ^RM -MOI
(R-I)
or a salt thereof, wherein
LG is a group that contains a protein binding moiety that is attached to P-N;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' are optionally joined to form a ring;
LLG3 is ^an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
LRG1 is ^-C (O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" are optionally joined to form a ring;
L ^RM is a linker;
The MOI is the moiety of interest.
[Aspect 17]
17. The method of aspect 16, wherein the targeting agent is or comprises an antibody agent.
[Aspect 18]
18. The method of aspect 17, wherein the moiety of interest selectively binds to said antibody agent at K246 or K248 of the IgG1 heavy chain, or a corresponding position.
[Aspect 19]
18. The method of aspect 17, wherein the moiety of interest selectively binds to said antibody agent at K251 or K253 of the IgG2 heavy chain, or a corresponding position.
[Aspect 20]
18. The method of aspect 17, wherein the moiety of interest selectively binds to said antibody agent at K239 or K241 of the IgG4 heavy chain, or a corresponding position.
[Aspect 21]
20. The method of claim 16, wherein the contacting and forming steps are performed in one chemical reaction.
[Aspect 22]
A composition comprising one or more compounds according to any one of aspects 1 to 15.
[Aspect 23]
1. A composition comprising:
Structure of Formula (P-II)
P-N-L ^PM -MOI (P-II)
A first compound having the formula:
P-N is a protein drug moiety containing a lysine residue;
L ^PM is a linker,
The MOI is the moiety of interest, a first compound,
The following structure:
LG-OH (LG-I)
wherein LG is a group that comprises a target binding moiety that binds to a targeting agent.
[Aspect 24]
Formula (RI)
LG-RG-L ^RM -MOI(R-I)
wherein LG is a group comprising a target binding moiety that binds to a targeting agent and is identical to LG in formula (LG-I);
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' are optionally joined to form a ring;
LLG3 is ^an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
LRG1 is ^-C (O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" are optionally joined to form a ring;
L ^RM is a linker and is the same as in formula (P-II);
The MOI is the moiety of interest, the third compound,
Formula (R-III)
HO-RG-L ^RM -MOI(R-III)
24. The composition according to aspect 23, further comprising a fourth compound having the formula:

Claims (24)

Formula RI :
LG-RG-L ^RM -MOI
(R-I)
[During the ceremony,
LG is a group that comprises a target binding moiety that binds to a targeting agent;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' may be connected to form a ring;
^LLG3 is an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
^LRG1 is -C(O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" may be joined to form a ring;
L ^RM is a linker;
MOI is the moiety of interest .
A compound having the structure: or a salt thereof. RG has the following formula :
is or comprises a reactive group having the formula
wherein ARYL is a substituted or unsubstituted para-phenylene ring;
The compound according to claim 1 or a salt thereof . ARYL is,
3. The compound of claim 2, or a salt thereof, having the structure: wherein ^Rs is independently selected at each occurrence from halogen, _-NO2 , -F, -L-R', -C(O)-L-R', -S(O)-L-R', -S(O) _2- L-R', and -P(O)(-L-R') ₂ , and R' is H or _C1 - _C6 alkyl. The reactive group has the following formula :
3. The compound according to claim 2, which is or comprises one of : RG has the following formula :
is or comprises a reactive group having the formula
wherein ARYL is a substituted or unsubstituted para-phenylene ring;
The compound according to claim 1 or a salt thereof . ARYL is,
wherein ^Rs is independently selected at each occurrence from halogen, -NO2, _-F , -L-R', -C(O)-L-R', -S(O)-L-R', -S(O) ₂ -L-R', and -P(O)(-L-R') ₂ , where R' is H or _C1 - _C6 alkyl;
The compound or salt thereof according to claim 5. The reactive group has the following formula :
6. The compound according to claim 5, which is or comprises one of : LG is R ^{LG -LLG} ,
^RLG is
R ^c -(Xaa)z-, a nucleic acid moiety, or a small molecule moiety;
each Xaa is independently a residue of an amino acid or amino acid analog;
t is 0 to 50;
z is 1 to 50;
each R ^c is independently -L ^a -R';
each L ^a is independently a covalent bond or an optionally substituted divalent group selected from C ₁ -C ₂₀ aliphatic or C _{1 -C 20} heteroaliphatic having 1 to 5 heteroatoms, wherein one or more methylene units of said group are optionally independently replaced with C(R') ₂ -, -Cy-, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ₂ -, -S(O) ₂ N(R')-, -C(O)S-, or -C(O)O- ;
each -Cy- is independently an optionally substituted divalent monocyclic, bicyclic, or polycyclic group, and each monocyclic ring is independently selected from a C _3-20 alicyclic ring, a C _6-20 aryl ring, a 5-20 membered heteroaryl ring having 1-10 heteroatoms, and a 3-20 membered heterocyclyl ring having 1-10 heteroatoms;
L ^LG is -L ^LG1 -, -L ^LG1 -L ^LG2 -, -L ^LG1 -L ^LG2 -L ^LG3 -, or -L ^LG1 -L ^LG2 -L ^LG3 -L ^LG4 -,
Each of L ^LG1 , L ^LG2 , L ^LG3 , and L ^LG4 is independently a covalent bond, or a divalent, optionally substituted, linear or branched C 1-100 group comprising one or more aliphatic moieties, aryl moieties, heteroaliphatic moieties each independently having 1 to 20 heteroatoms , heteroaromatic moieties each independently having _{1 to 20} heteroatoms, or any combination of any one or more of such moieties, wherein one or more methylene units of said group are independently selected from C _1-6 alkylene, C _1-6 alkenylene, a divalent C _1-6 heteroaliphatic group having 1 to 5 heteroatoms, -C≡C-, -Cy-, -C(R') ₂ -, -O-, -S-, -S-S-, -N(R')-, -C(O)-, -C(S)-, -C(NR')-, -C(O)N(R')-, -C(O)C(R') ₂ N(R')-, -N(R')C(O)N(R')-, -N(R')C(O)O-, -S(O)-, -S(O) ₂ -, -S(O) ₂ may be replaced by N(R')-, -C(O)S-, -C(O)O-, -P(O)(OR')-, -P(O)(SR')-, -P(O)(R')-, -P(O)(NR')-, -P(S)(OR')-, -P(S)(SR')-, -P(S)(R')-, -P(S)(NR')-, -P(R')-, -P(OR')-, -P(SR')-, -P(NR')-, an amino acid residue, or -[(-O-C(R') ₂ -C(R') ₂ -) _n ]- (wherein n is 1 to 20) ;
each R' is independently -R, -C(O)R, -CO ₂ R, or -SO ₂ R;
each R is independently -H or an optionally substituted group selected from _C1-30 aliphatic, C1-30 heteroaliphatic having 1-10 heteroatoms, _C6-30 aryl, _C6-30 arylaliphatic, _C6-30 arylheteroaliphatic having 1-10 heteroatoms, _5-30 membered heteroaryl having 1-10 heteroatoms, and 3-30 membered heterocyclyl having 1-10 heteroatoms; or two R groups may independently be joined together to form a covalent bond ; or two or more R groups on the same atom may independently be joined together to form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having 0-10 heteroatoms in addition to said atom; or two or more R groups on two or more atoms may independently , together with their intervening atoms, form an optionally substituted 3-30 membered monocyclic, bicyclic, or polycyclic ring having , in addition to said intervening atoms, 0-10 heteroatoms;
The compound according to claim 1 or a salt thereof . 2. The compound or salt thereof of claim 1, wherein LG is or comprises a target binding moiety that binds to a targeting agent, and the targeting agent is an antibody agent. 2. The compound or salt thereof according to claim 1, wherein LG is or comprises a target binding moiety that binds to an Fc region, and/or ^RLG is or comprises DCAWXLGELVWCT (SEQ ID NO: 2), wherein the two cysteine residues may form a disulfide bond, and X is an amino acid residue. The following conditions :
(a) the moiety of interest is or comprises a therapeutic agent;
(b) the moiety of interest is or comprises a moiety capable of binding to a protein, a nucleic acid, or a cell; and/or (c) the moiety of interest is or comprises a reactive moiety suitable for a bioorthogonal reaction.
The compound or salt thereof according to claim 1, wherein at least one of the following is satisfied: LG is represented by the formulas A-1 to A-50 :
2. The compound of claim 1, or a salt thereof , which is or comprises a target binding moiety having a structure selected from: 2. The compound or salt thereof of claim 1, wherein the MOI is or comprises a therapeutic drug moiety and/or the MOI is or comprises an antibody drug. The compound or salt thereof according to claim 1, wherein ^LRM comprises one or more -[(CH ₂ ) _n -O] _m -, each n independently being 1 to 20 and m being 1 to 100. In formula (R-I),
the targeting agent is an antibody comprising an IgG heavy chain comprising K246 or K248;
2. The compound or salt thereof of claim 1, wherein the target binding moiety is configured to bind to the antibody in a manner that brings the reactive group into proximity with K246 or K248 of the IgG heavy chain to allow reaction between K246 or K248 and the reactive group, resulting in binding of a moiety comprising an ^LRM -MOI to K246 or K248 and removal of the group containing the target binding moiety from the compound or salt thereof . P-I :
P-L ^PM -MOI
(P-I)
[During the ceremony,
P is a targeting drug moiety;
L ^PM is a linker,
MOI is the moiety of interest.
or a salt thereof, comprising the steps of:
1) A targeting agent and a compound of formula R-I :
LG-RG-L ^RM -MOI
(R-I)
[During the ceremony,
LG is a group that comprises a target binding moiety that binds to a targeting agent;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' may be connected to form a ring;
^LLG3 is an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
^LRG1 is -C(O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" may be joined to form a ring;
L ^RM is a linker;
MOI is the moiety of interest .
or a salt thereof ;
2) forming a compound having the structure P-I or a salt thereof ;
A method comprising:
Or P-II :
P-N-L ^PM -MOI
(P-II)
[During the ceremony,
P-N is a protein drug moiety containing a lysine residue;
L ^PM is a linker,
MOI is the moiety of interest.
or a salt thereof, comprising the steps of:
P-N and a compound of the formula R-I :
LG-RG-L ^RM -MOI
(R-I)
[During the ceremony,
LG is a group that contains a protein binding moiety that is attached to P-N;
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' may be connected to form a ring;
^LLG3 is an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
^LRG1 is -C(O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" may be joined to form a ring;
L ^RM is a linker;
MOI is the moiety of interest .
or a salt thereof with a reaction partner having the structure : The method of claim 16, wherein the targeting agent is or includes an antibody agent. The method of claim 17, wherein the moiety of interest selectively binds to the antibody drug at K246 or K248, or a corresponding position, of the IgG1 heavy chain. The method of claim 17, wherein the moiety of interest selectively binds to the antibody drug at K251 or K253, or a corresponding position, of the IgG2 heavy chain. The method of claim 17, wherein the moiety of interest selectively binds to the antibody drug at K239 or K241, or a corresponding position, of the IgG4 heavy chain. The method of claim 16, wherein the contacting step and the forming step are performed in one chemical reaction. A composition comprising one or more compounds or salts thereof according to any one of claims 1 to 15. 1. A composition comprising:
Formula (P-II) :
P-N-L ^PM -MOI (P-II)
[During the ceremony,
P-N is a protein drug moiety containing a lysine residue;
L ^PM is a linker,
MOI is the moiety of interest .
or a salt thereof ,
structure :
LG-OH (LG-I)
where LG is a group that contains a target binding moiety that binds to a targeting agent .
or a salt thereof ; and
A composition comprising: Formula (RI) :
LG-RG-L ^RM -MOI(R-I)
[During the ceremony,
LG is a group containing a target binding moiety that binds to a targeting agent, and is the same as LG in formula (LG-I);
RG is a reactive group of the formula ^-LLG2 - ^LLG3 - ^LLG4 - ^LRG1 - ^LRG2- ;
L ^LG2 is -NH-C(O)O-C(R') ₂ -, where each R' is independently H or C1-C10 alkyl, and R' may be connected to form a ring;
^LLG3 is an optionally substituted aryl ring;
L ^LG4- is -NH- or -O-;
^LRG1 is -C(O)-, -S(O)-, -OS(O) ₂ -, or -OP(O)(OR) ₂ -;
L ^RG2 - is a covalent bond or [-C(R") ₂ C(R")=C(R)]C(O)-, where each R" is independently H or C1-C10 alkyl, and any two R" may be joined to form a ring;
L ^RM is a linker and is the same as L ^RM in formula (P-II);
MOI is the moiety of interest .
or a salt thereof ; or
Formula (R-III) :
HO-RG-L ^RM -MOI(R-III)
or a salt thereof;
or a combination thereof.