WO1996023775A1 - Novel pyridonecarboxylic acid derivatives or salts thereof and antibacterial agent containing the same as active ingredient - Google Patents

Abstract

A pyridonecarboxylic acid derivative represented by general formula (1) or a salt thereof and an antibacterial agent containing the same, wherein R1 represents hydrogen or a carboxy protecting group; R2 represents nitro or optionally substituted amino; R3 represents halogeno; R?4 and R5¿ may be the same or different and each represents hydrogen, halogeno, lower alkyl or lower alkoxy; R6 represents hydrogen, halogeno, hydroxy, lower alkyl or amino; R7 represents hydrogen or halogeno; A represents nitrogen or -CX= (wherein X represents hydrogen, halogeno, lower alkyl or lower alkoxy); and Z represents halogeno or optionally substituted, saturated cyclic amino.

Description

 Specification

 Novel pyridone carboxylic acid derivative or salt thereof and antibacterial agent containing the substance as active ingredient

 The present invention relates to a novel pyridone carboxylic acid derivative or a salt thereof having excellent antibacterial activity and oral absorption, and an antibacterial agent containing the same.

 Background art

 Many of the compounds having pyridone carboxylic acid as a basic skeleton have excellent antibacterial activity and a broad antibacterial spectrum, and are therefore useful as synthetic antibacterial agents. Are known. Among them, among these, there are nonolefloxacin (JP-A-53-141286), enoxacin (JP-A-55-31042), and Floxacin (Japanese Unexamined Patent Publication No. 57-46986), Siplofloxacin (Japanese Unexamined Patent Application Publication No. 58-76667), Tosflokisaki (Japanese Patent Application Laid-Open No. 60-222,479) are widely used in the clinical field as therapeutic agents for infectious diseases.

 However, these compounds were still inadequate in terms of antibacterial activity, intestinal absorption, metabolic stability, and side effects, particularly phototoxicity and cytotoxicity.

Disclosure of the invention

The present invention has been made in view of the above circumstances, and is a novel pyridone carbonyl that satisfies antibacterial activity, intestinal absorption, metabolic stability and side effects, particularly phototoxicity and cytotoxicity. Acid derivatives or And an antibacterial agent containing the same.

 In view of such circumstances, the present inventors have conducted intensive studies to obtain a compound that can be a clinically excellent synthetic antibacterial agent. As a result, the compound represented by the following general formula (1) was converted to a compound represented by the following formula: The present inventors have found that they have excellent antibacterial properties against negative bacteria and Gram-positive bacteria, are extremely low-toxic and are useful as synthetic antibacterial agents, and have accomplished the present invention. It is a thing.

 That is, the present invention provides the following general formula (1)

(In the formula, R ¹ represents a hydrogen atom or a carboxyl protecting group, R ² represents a nitro group or a substituted or unsubstituted amino group, and R ³ represents a halogen atom. R ⁴ and R ⁵ are the same or different and may be a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, and R ⁶ is a hydrogen atom, a halogen atom R ⁷ represents a hydrogen atom or a halogen atom, A represents a nitrogen atom or —CX = (here, X represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group), and Z represents a halogen atom or It represents a saturated cyclic amino group which may have a substituent. A pyridone carboxylic acid derivative or a salt thereof represented by the formula:

 The present invention also provides an antibacterial agent containing the pyridone carboxylic acid derivative or a salt thereof as an active ingredient.

 BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in more detail. The term “lower” in the substituent of the pyridone carboxylic acid derivative represented by the above general formula (1) of the present invention means that when the substituent is a chain, it has 1 carbon atom. The compounds having 1 to 7 carbon atoms are preferred, and those having 1 to 5 carbon atoms are particularly preferable. When they are cyclic, those having 3 to 7 carbon atoms are meant.

In the above general formula (1), the carboxyl protecting group represented by R ′ is an ester residue of a carboxylate ester, which is relatively easily cleaved to give a corresponding free radical. Examples are those which generate a carboxyl group, and specific examples thereof include a methyl group, an ethyl group, an n-propyl group, an i-propyl group, and an n-butyl group. Groups, i — butynole group, t — lower alkyl group such as butynole group, pentyl group, hexyl group, heptyl group; vinyl group, aryl group, 1-propyl group, butenyl group, phenyl group Lower alkenyl groups such as phenyl, hexeninole and heptenyl; aralkyl having 7 to 11 carbon atoms such as benzyl; and 6 to 1 carbons such as phenyl and naphthyl. By treating under mild conditions such as hydrolysis and catalytic reduction of aryl groups, etc. Which release, or § Se Bok key sheet methylation group, such Bibaro Lee Ruoki shea methylation group lower Lower alkyl groups such as alkanoloxy lower alkyl groups; lower alkoxy groups such as methoxycarbonyl carbonyloxymethyl groups and 1-ethoxycarboxylic carbonyloxy groups; A lower alkoxy lower alkyl group such as a methoxymethyl group; a lactonyl group such as a phthalidyl group; a di-lower alkylamino lower alkyl group such as a 1-dimethylaminoethyl group; (5_methyl—2—oxo 1, 3—dioxonor 4—inole) Examples thereof include those which are easily eliminated in vivo such as a methyl group. In addition, a hydrogen atom is particularly preferable as R ¹ .

Examples of the substituent in the substituted amino group represented by R ² include a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butynole group, and i- Butynole group, t-butynole group, pentyl group, hexyl group, heptyl group and other lower alkyl groups; vinyl group, aryl group, 1-propeninole group, butenyl group, phenyl group Lower alkenyl groups such as benzyl, hexenyl and heptenyl; alkenyl having 7 to 11 carbon atoms such as benzyl and 1-phenylethyl; phenyl A C6-C14 aryl group such as a naphthyl group or a naphthyl group; a honoleminole group, an acetyl group, a propionyl group, a butyryl group, an isobutylinole group, etc. Lower alkanol groups; lower alkyl groups such as methoxycarbonyl and ethoxycarbonyl groups; Xylonolebonyl group; Benzoyl group, naphthoyl, etc. C7-C15 aryl group; Glycinole, Mouth Ixinole, Noxinolole, Alara Families such as ginore, feninore alaninore, araninore araranil, glycirl varinole, grisill glycirl Acid residues or oligopeptide residues and their Amino acid residue or oligopeptide residue whose functional group is protected by a commonly used protecting group in peptide chemistry such as acyl group or lower aralkyl, or cyclic amino group Group. These substituents can be arbitrarily selected from one or two same or different substituents. Compounds protected with such amino acid residues or peptide residues are expected to have improved water solubility o

More preferred R ² is an amino group, a lower alkylamino group, a di-lower alkylamino group, a lower alkanoinorea amino group, an amino acid-substituted amino group, and an oligo group. Gopeptide-substituted amino groups. More preferred examples of R ² include an amino group, a methylamino group, an ethylamino group, a dimethylamino group, a holinoamino group, Glycine amino group, loycin amino group, norino amino group, aranyl amino group, aranyl alanyl amino group, and the like. Of these, amino groups are particularly preferred.

Examples of the halogen atom represented by R ³ , R ⁴ , R ⁵ , R ^6, and R ⁷ include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. A fluorine atom or a chlorine atom is preferred, and a fluorine atom is particularly preferred.

Examples of the lower alkyl group represented by R ⁴ , R ⁵ , R ⁶ and X include a methylenol group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, t A monobutyl group, a pentyl group, a hexyl group, a heptyl group, and the like, with a methyl group being preferred. As a lower alkoxy group represented by R ⁴ , R ⁵ and X Examples thereof include a methoxy group, an ethoxy group, an n-propoxy group, an n-butoxy group, a t-butoxy group and the like.

Preferred combinations of R ⁴ and R ⁵ are a halogen atom and a hydrogen atom, and more preferably, R ^{4 is a} fluorine atom or a chlorine atom and R ⁵ is a hydrogen atom. It is particularly preferred that R ^{4 is a} fluorine atom and R ⁵ is a hydrogen atom. Note that this R ⁴ is the same as R ² . It is particularly preferable to substitute at position l.

 Examples of the halogen atom represented by X and Z include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and a fluorine atom and a chlorine atom are particularly preferred.

 Further, the compound of the formula (1) has a naphthyridine skeleton when A represents a nitrogen atom, and has a quinoline skeleton when A represents —CX =. However, it is particularly preferred that A represents a nitrogen atom and that —CC 1 =.

The saturated cyclic amino group which may have a substituent represented by Z further contains one or more hetero atoms such as a nitrogen atom, an oxygen atom, an thio atom and a carbonyl carbon atom in the ring. And may be monocyclic or bicyclic or tricyclic. Preferred is a 4- to 7-membered ring for a monocyclic ring, a 7 to 11-membered ring for a bicyclic ring, and a 9 to 15-membered ring for a tricyclic ring. Examples of such cyclic amino groups include, for example, aziridin-1—yl, azetidin-11-inole, pyrrolidine-11-inole, and pyridinone. 1 Saturated monocyclic 3- to 7-membered cyclic amino group having one nitrogen atom such as 1-yl; for example, pyrazine-1-1-inole, homopiperazine — 1 — Saturated monocyclic having two nitrogen atoms such as 7-membered cyclic amino group; for example, oxazolidin-13-yl, monoleforin-14-inole, thiazolidin-11-inole, thiomololin-4-4-y Saturated monocyclic 3- to 7-membered cyclic amino group having a heteroatom selected from an oxygen atom and a sulfur atom in addition to a nitrogen atom such as thiol; for example, tetrahydroquinoline 1—Saturated 2- to 3-cyclic cyclic amino group such as ethyl; for example, 2,8-diazaspiro [4.4] nonan 1 2—inole, 5—azaspiro [2. 4] Heptane-1 5 _yl, 7-Azabicyclo [2.2.1] Heptane 1 7-Innole, 2, 8-Jazabicyclo [4.3.0] Nonan 1-8 Nore, 5 — Methinole 2, 5 — Jazabicyclo [2.2.1] Heptane 1 2 — Ginore, 2, 5 — Jazabicyclo 2.2.1] Heptane-1 2-phenol, 3, 8-diazabicyclo [3.2.1] octane 13-spiro and cross-linked Examples thereof include a saturated 5- to 12-membered cyclic amino group.

 The atoms constituting the ring of these saturated cyclic amino groups may be substituted with an appropriate substituent. Examples of such a substitutable group include, for example, hydrogen. Xyl group, lower alkyl group, substituted or unsubstituted amino group, substituted or unsubstituted amino lower alkyl group, lower alkoxy group, halogen atom, etc. ο

Here, the lower alkyl group which can be substituted for the saturated cyclic amino group includes, for example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, and a heptyl group. A group having 1 to 7 carbon atoms, such as a group, is a lower alkoxy group. C 1 to C 7, such as a group, an ethoxy group, and an n-propoxy group, include halogen atoms such as a fluorine atom, a chlorine atom, and a bromine atom. . Among the substituents on the saturated cyclic amino group, the substituents on the substituted amino group and the substituted amino lower alkyl group are the same as those represented by R ^2. Particularly preferred examples of the substituted amino group and the substituted or unsubstituted amino lower alkyl group include a methylamino group and an ethylamino group. Group, dimethylamino group, aminomethyl group, 1-aminoethyl group, 2—aminoethyl group, 1-amino-1—ethyl group, methylamino Methyl group, methyl amino group, methyl amino group, methyl group, amino group, mouth amino group, valley Examples include a non-amino group, an aranil-amino group, an aranyl-a-nitro-amino group, and the like. .

 Among these saturated cyclic amino groups, preferred groups include those represented by the following formulas (a) and (b).

 (a) (b)

[In the formula, Y represents an oxygen atom, a sulfur atom or NR ⁸ (where R ⁸ represents a hydrogen atom or a lower alkyl group), and e represents 3 to 5 Shows the number, f is indicates the number of 1 ~ 3, g is indicates the number of ^{0 ~ 2, J l, J} 2 and J ³ is rather good be the same or different Ttei, hydrogen atom, arsenic (Indicates droxyl group, lower alkyl group, amino lower alkyl group, amino group, lower alkylamino group, lower alkoxy group, and halogen atom.)

In the formulas (a) and (b), the lower alkyl group, amino lower alkyl group, lower alkylamino group, lower alkoxy group, and halogen atom are those represented by R ² to those similar to the groups shown by R ⁵ is exemplified.

 Examples of the cyclic amino group represented by the formula (a) include azetidin-11-yl group, pyrrolidine-11-yl group, and piberidine-1 And the cyclic amino group represented by the formula (b) includes, for example, a pyrazine-11-inole group, a morpholin-14-inole group, Thiomolephosphorin-14-inole group, homopirazine-1-1-inole group, N-thiazolidinyl group, N-oxazolidinyl group, etc. . Of these, a cyclic amino group represented by the formula (a) is more preferred, and an azetidin-1-yl group or a pyrrolidine-11-yl group is particularly preferred.

 Particularly preferred specific examples of the groups represented by the formulas (a) and (b) are as follows.

3 — Aminoazetidine-1 1 — Inole group, 3 — Methylaminoazetidine 1 — Inole group, 3 — Dimethylaminoazetidine -1-ethyl group, 3-aminomethylazetidine 1-amino group, 3-amino 2-methylazetidine 1-1-inole group, 3 — Amino 1 3 — Methyl azetidin 1 1 — Inole group, 3 — Alaninole 1-amino-azetidine- 1-yl group, 3-phenol- 1-amino-azetidine 1-yl group, pyrrolidine- 1-yl group, 3 -Hydroxypyrrolidine-1 -yl group, 3,4 -Hydroxypyrrolidine-1 1 -Inole group, 3 -Methoxypropyl Gen 1 -yl group, 3-Methyl phenol pyrrolidine 1-1-Inole group, 3 -Hydrogen D xyl-4-Methyl phenol pyrrolidine 1-1 -yl group , 3-amino resin 1-inole group, 3-methyl amine □ 1-amino group, 3-dimethyl amino pyridine 1-yl group, 3—ethyl aminopyrrolidine — 1—yl group, 3—ethyl amino pyrrolidine, 1—yl group, 3 — ミ チ レ リ 1 1 — 1 3 groups, 3-amino-3, methylyl resin, 1-yl group, 3—amino, 4-methyl-pyrrolidine, 11-yl group, 3 — Amino 5 — Methyl pyrrolidin 11-yl group, 3 — Methyl amino 1 4 — Methyl pyrrolidine 11-yl group, 3 — Dimethylamine 4- 1-methylpyrrolidin 11-yl group, 3-ethylaminopyrrolidin 4-111 methylpyrrolidin 11-yl group, 3 — Genoreamino 1-yl 3-,-methylinopyrrolidine 11-yl group, 3 — Genoinoleino 1-4-,-methylo-pyrrolidin 11-yl group, 3 — Aminomethyl pyrroleine 1-yl, 3—Methylenolyl pyrrolidine 1-yl, 3—Methylenol pyrrolidine 1-yl Group, 3 — dimethino Aminomethyl group 4-Methylpyrimone 1-yl group, 3—Ethylaminomethyl group 41-Methylazole pyrrolidine—1 ーYl group, 31 (1—aminoethyl) 1-4-methyl pyrrolidinine 1—yl group, 3- (2—aminoethyl) 1-4—me Chinole pyrrolidine — 1 — yl group, 3 — amine Ethylpyrrolidin 1-yl group, 3-methylaminoamine 4—Ethynylpyrrolidin 1-1-yl group, 3—Dimethylamine 4-ethylpyrrolidine- 1-yl group, 3-ethylen-pyrroleamine- 1-yl group, 4-ethylen-pyrrolidine- 1-yl group, 3-diethylamino 14-ethyl pyrrolidine 1-dynole group, 3—amino pyridine 1-d-pyrrolidine 11-yl group, 3—methyla Minomethyl 4 — Ethynylpyrrolidin 1-yl group, 3 -dimethylaminomethyl 4 — Ethynolepiperin-1- 3-, 3-amino-1,3-methylpyrrolidin, 3-, 3-methylamino-3, 3-methylpyrrolidin Group, 3 — dimethyla Mino 3 — methyl resin mouth resin group 3 — Amino 3, 4 — Dimethyl resin mouth resin group 3 — amino 4 , 4-Dimethyl olefin resin ring 3-amino 4, 5-Dimethyl olefin resin ring 1-3-amino 2, 4- Dimethyl benzoyl group 3 — methyl amine 3, 4 — dimethyl pyrrolidine 1 — yl group, 2-methyl group 3 — Aminobi D resin 1-1yl group, 2 — Methyl 3 — Dimethyl benzoylamine pyrrolidine 11-yl group, 3-amino 4—Methoxy pyridine 1-yl group, 3—Aryl phenol 1-yl group, 3—Pyrrolidine 1-yl group, 3—N-amino group Pyrrolidine-1 1-inole group, Brazil 1-yl group, 4—methyl-biperazine 1-yl group, 3—methyl-biperazine 1-yl group, 2—methyl pyrazine Ginyl 1-yl group, 3,4-Dimethylinviperazine 1-yl group, 3, 5—Dimethylinylbiperazine 11-yl group, 3 , 3 — Dimethinole Biperadine 1 -Inole group, 3, 4, 5 — Trimethylinolepiperazine-1 1-Inole group, pyridin 11 1-isole group, 4-aminophenol 1-yl group, 4-methylaminopyridine piperidine 1-vinyl group, 4-hydroxypiperidine 1-vinyl group, mono-ole group 4-methyl group, 2 — amide methyl mono- holene 1-4-inole group, 2-methyl amide amino holene 4-inole group, 2 — 4-methyl group, thiom-l-yl 4-methyl group, thiom-pyrazine-l 4-yl group, 4-methyl group Tyl homopiperazine 1-inole group, N — thiazolidinyl group, N — oxazolidininole group.

In the general formula (1), preferred Ri yo correct ^{R ', R 2, R 3} , R 4, R 5, R 6, a combination of R ^7, A and Z, R' is a hydrogen atom; R ² Gaa Mi R ³ , a lower alkylamino group, a di-lower alkylamino group, a lower aminophenol amino group, an amino acid-substituted amino group or an oligopeptide-substituted amino group; R ³ Is a halogen atom; R ^{4 is a} halogen atom; R ⁵ is a hydrogen atom; R ⁶ is a hydrogen atom; R ⁷ is a fluorine atom; A is a nitrogen atom; — CH = or — CC 1 =; This is the case when Z is a group represented by the formula (a). Further preferred correct ^{R ', R 2, R 3} , R 4, R 5, R 6, a combination of R ^7, A and Z, R ¹ is a hydrogen atom; R ² Gaa Mi amino group; R ³ power off Tsu atom or a chlorine atom: R ⁴ gaff Tsu (substituted at the para-position relative to R ²⁾ atom or a chlorine atom; R ⁵ is a hydrogen atom; R ⁶ is a hydrogen atom; R ⁷ power off Tsu atom; a is nitrogen Atom or one CC 1 =; Z is a group (e = 3 or 4) represented by the formula (a).

Pyridonic carboxylic acid derivatives or their salts (1) are acid addition salts Alternatively, both base addition salts can be formed. In addition, this salt also includes those which form a chelate salt with a boron compound. Examples of the acid addition salts include (A) salts with mineral acids such as hydrochloric acid and sulfuric acid, and (B) formic acid, citric acid, trichloroacetic acid, trifluoroacetic acid, and fumaric acid. Salts with organic acids such as acids and maleic acids, such as (C) methansulphonic acid, benzenesulphonic acid, p-trinorenence norephonic acid, Examples of salts with sulfonic acids such as mesitylenesorenoic acid and naphthalenesulfonate, and examples of the base addition salts include, for example, (A ') sodium Salt with an alkaline metal such as limestone, salt with an alkaline earth metal such as (B ') canolemium, magnesium, and (C') aluminum. Ammonium salt, (D ') trimethylamine, triethylamine, tributinoreamin, pyridin, N, N—dimethinorea Lin, N — Methyl oleperidine, N — Methyl mono olein, Jethylamine, Cyclohexamine, Proline, J Benzenoremin, N — Benzenore 1/3 — phenamine, 1 — phenamine, N, N '— diphenylamine Salts with nitrogen-containing organic bases such as amines can be mentioned. In addition, examples of the boron compound include boron halide such as boron fluoride, and lower alkoxyboron such as acetate boron.

The pyridone carboxylic acid derivative or a salt thereof (1) can exist not only in an unsolvated form but also as a hydrate or solvate. Accordingly, the compounds of the present invention include all of their crystal forms and hydrates or solvates. The pyridone carboxylic acid derivative or its salt (1) can be present as an optically active substance. These optically active substances are also included in the compound of the present invention. Further, the compound (1) may exist as different stereoisomers (cis type, trans type). These stereoisomers are also included in the compounds of the present invention.

 The pyridone carboxylic acid derivative or a salt thereof (1) is produced by an arbitrary method corresponding to the type of the substituent and the like, and examples thereof include the following. That's it.

(Step 1) Among the compounds represented by the general formula (1), a compound in which R ¹ is a hydrogen atom or a lower alkyl group and Z is a halogen atom can be produced, for example, by the following reaction formula It is manufactured by a series of process 1 represented by

(B) COOR Nito

[Wherein, R'a represents a lower alkyl group, R ⁹ represents ^a lower alkoxy group or a group _NR ¹² R ¹³ (where R ¹² and R ' ³ each represent a lower alkyl group. ) Indicates R '. And R indicates a lower alkyl group, respectively, L ¹ is shows the C b gain down atom, Z 'is indicates Ha B gain down atom, R ^2a is shows the substitution A Mi amino group, R ^2, R ³ , R ⁴ , R ^s , R ⁶ , R ⁷ and A have the same meaning as described above.)

That is, the compounds (1a) and (1d) of the present invention are obtained by reacting the compound (A) with an orthoformate ester (H) such as ethyl orthoformate or methyl orthoformate. (J) is reacted, then cyclized, and the resulting compound (C) is converted into a compound (la) by dibolation, and reduced to give a compound (lb) The compound (1c) is obtained by alkylating or acylating the compound, and the compound (1d) is obtained by hydrolyzing it. Also, compound (Id) can be obtained by hydrolyzing compound (lb).

 The reaction between the compound (A) and the orthoformate ester (H) is usually carried out at 0 to 160 ° C., preferably at 50 to 150 ° C., and the reaction time is usually 10 minutes. ~ 48 hours, preferably 1-10 hours. The amount of the orthoformate used is preferably at least equimolar to the compound (A), especially about 1 to 10 moles per mole of the compound (A).

The reaction with the compound (J) is carried out without a solvent or in a suitable solvent. It is also desirable to add a carboxylic anhydride such as acetic anhydride as a reaction aid. The solvent used herein may be any solvent that does not affect the reaction, and examples thereof include aromatic hydrocarbons such as benzene, toluene, and xylene. Any ethers such as diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme; pentane, hexane, heptane And aliphatic hydrocarbons such as ligroin; halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride; dimethylformamide And non-protonic polar solvents such as dimethinoresolelefoxide; methanol, ethanol, and prono. Examples of alcohols such as knoll. This reaction is usually performed at 0 to 150 ° C, preferably at 0 to 100 ° C, and the reaction time is usually 10 minutes to 48 hours. Compound (J) The amount of the compound to be used is at least equimolar to the compound (A), preferably from equimolar to 2 times mol.

 Alternatively, compound (A) may be added to compound (A) such as N, N—dimethylformamide dimethinoreacetanol, and N—dimethylinoformolamide, etc. After reacting the compounds, compound (J) can be reacted to lead to compound (B). As the solvent used for the reaction with the acetals, any solvent that does not affect the reaction may be used, and examples thereof include those described above. This reaction is usually performed at 0 to 150 ° C, preferably at room temperature to 100 ° C, and the reaction time is usually 10 minutes to 48 hours, preferably 1 to 10 hours. is there.

Compound (B) is subjected to a cyclization reaction to give compound (C). This reaction is performed in a suitable solvent in the presence or absence of a basic compound. As the solvent used in this reaction, any solvent can be used as long as it does not affect the reaction.Examples include aromatic hydrocarbons such as benzene, toluene and xylene. Hydrogens; ethynoleate, ethers such as tetranofuran, dioxane, monoglyme; methylene chloride, black mouth holm, tetrachloride Halogenated hydrocarbons such as carbon: methanol, ethanol, prono. Examples include alcohols such as phenol and butanol; and non-protonic polar solvents such as dimethyl sulfonamide and dimethyl sulfoxide. Alkali metals such as sodium metal, potassium metal, etc .; hydrogenated sodium, hydrogenated calcium; Such as metal water Inorganic salts such as sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate; sodium methoxide, sodium Any phanolexide, such as trimuet or calcium, t-butoxy; sodium fluoride, calcium fluoride, etc. Any metal fluorides; triethylamine, 1,8-diazabicyclo [5.4.0], and any organic salts such as pendene (DBU). The reaction temperature of this reaction is usually 0 to 200 ° C, preferably room temperature to 180 ° C, and the reaction is usually completed in 5 minutes to 24 hours. The amount of the basic compound to be used is 1 mol or more, preferably 1 mol to 2 mol, per 1 mol of compound (B).

 The compound (1a) of the present invention can be produced by subjecting the compound (C) to a nitration reaction. Nitrogenation is performed by a general method used for dinitrogenation of aromatic compounds. As the nitrifying agent, nitric acid or a mixed acid obtained by combining nitrate and sulfuric acid is used. And acetyl nitrate. The amount of the mixed acid used for the reaction is 1 equivalent to a large excess of sulfuric acid and 1 equivalent to a large excess of nitric acid with respect to 1 equivalent of the compound (C). This is done by adding (C). The reaction temperature is 110 ° C to 80 ° C. C ヽ The reaction time is preferably 5 minutes to 5 hours.

 Compound (1b) can be obtained by reducing compound (1a).

For the reduction, a commonly used method can be used. For example, a solution using zinc, iron, soot, soot (II) chloride or the like in an acidic solution can be used. Metalolytic reduction, reduction using sodium sulfide, such as sodium sulfide, sodium hydrosulfide, and sodium dithionite, and platinum and Raney nickel , Platinum-black (Pt-C), palladium carbon (Pd-C) and the like.

The compound (1d) in which R ¹ is a hydrogen atom is obtained by hydrolyzing the compound (1b) or, if desired, alkylating or acylating the compound (lb). It can be obtained by disassembly.

 The hydrolysis can be performed under any of the reaction conditions used in ordinary hydrolysis reactions. Examples include sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. Basic compounds, such as minerals: mineral acids such as hydrochloric acid, sulfuric acid, and hydrobromic acid; or

In the presence of organic acids such as P-toluenesulfonate, water, methanol, ethanol, propanol, and other phenolic compounds, tetrahydrofuran Solvents such as ethers such as lan and dioxane, ketones such as acetone, methylethylketone, acetic acid, etc., or a mixed solvent thereof. Done. This reaction is usually carried out at room temperature to 180. C, preferably at room temperature to 140 ° C, and the reaction time is usually 1 to 24 hours.

The alkylation reaction for obtaining the compound (1C) of the present invention is carried out by using an anoalkylating agent such as dialkyl sulfate, alkyl chloride, alkyl bromide or the like, preferably sodium carbonate, corresponding to a desired alkyl group. In the presence of a base such as lithium or potassium carbonate, in a solution such as N, N-dimethylformamide, N-methizolepyrrolidone, room temperature to 150 ° C Reacts with the compound (1b) at about You can do it. This alkylation reaction is carried out in the presence of a carbonyl compound corresponding to the desired alkyl group, followed by a catalytic reduction method using platinum, Raney nickel, platinum black, and palladium carbon. You can also do this. The acylation reaction can be carried out by any of the reactions commonly used for acylation of amino groups, such as acyl chloride corresponding to the desired acyl group. Or an acid anhydride and a compound (lb) are converted into halogenated hydrocarbons such as methylene chloride, chlorophonolem, carbon tetrachloride, and chlorobenzene; benzene, Aromatic hydrocarbons such as toluene; ethers such as tetrahydrofuran and dioxane; or acetate trinoles, N, N—dimethinolehonolemamide Pyridin, picolin, N, N-dimethylaniline, N-methylmorpholin, dimethinoreamin at 0 ° C to room temperature in nonprotonic polar solvents such as In the presence or absence of a base such as triethylamine, sodium carbonate, carbonated rim, etc. To

-By reacting at 70 to 100 ° C, or by reacting an acid such as formic acid or acetic acid or an acid anhydride thereof at room temperature to 150 ° C. You can also do this.

In general formula (1) compound is a medium R ⁶ Gaa Mi amino group is in the child that is the reaction using and R ⁶ Gaha b compound is gain down atom (A) as a starting material After obtaining the compound (la), (lb), (1c) or (Id), the halogen atom is preferably obtained by subjecting the halogen atom to amino elimination.

Also, the compound (1 b) is Ru can this and the force ^"5 also be synthesized in Tsu by the following methods. Condensation and cyclization

[In the formula, R ¹⁴ represents an amino protecting group, and R ′ ^a , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ^s , L ′, Z ′ and A are as defined above. That is, acrylate esters (D) obtained by reacting the above-mentioned compound (A) with orthoformates (H) and phenyl. The compound (L) is obtained by condensing and cyclizing a range amine (K), and then the compound (lb) is obtained by removing the amino-protecting group. ) Can be obtained.

 The reaction for obtaining the compound (L) from the compound (A) can be carried out under the same conditions as the above-mentioned reaction for obtaining the compound (C) from the compound (A).

Elimination of amino protecting groups (mainly acyl and carbamoyl) Is carried out by hydrolysis with an acid or an anolyte. This condition is the same as that described for the hydrolysis to compounds (lb) and (lc) above.

 (Step 2) — Among the compounds represented by the general formula (1), a compound in which Z is a saturated cyclic amino group optionally having a substituent is represented by, for example, the following reaction formula Manufactured by Step 2.

 (N) (0)

[In the formula, Z ² represents a saturated cyclic amino group which may have a substituent, and R ′, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , Z ¹ And A have the same meaning as above.)

That is, the compound (0) can be obtained by aminating the compound (N) with a compound represented by the formula Z ² —H.

This reaction is carried out using any aromatic hydrocarbons such as benzene, toluene, xylene, etc .; any phenols such as methanol, ethanol, etc .; Any ethers such as transhydran, dioxane, monoglyme; such as methylene chloride, chloroform, carbon tetrachloride Halogenated hydrocarbons; non-protonic, such as dimethyl alcohol, dimethyl alcohol, dimethyl alcohol, N-methyl pyrrolidone Polar solvent; In a solvent that does not affect the reaction, such as toluene and pyridin, a deoxidizing agent, if necessary, such as sodium carbonate, calcium carbonate, sodium hydrogen carbonate Um, triethylamine, 1,8-diazabicyclo [5.4.0] This is carried out at room temperature to 160 ° C in the presence of dendecene (DBU). The reaction time is a few minutes to 48 hours, preferably 10 minutes to 24 hours. The amount of compound Z ² —H to be used is preferably equimolar or more, preferably equimolar to 5 times mol, relative to compound (N). When R ¹ is a carboxyl protecting group, it can be converted to a hydrogen atom by hydrolysis as desired.

(Step 3) — Among the compounds represented by the general formula (1), the compound in which R ¹ is a carboxyl protecting group is produced, for example, by Step 3 shown in the following reaction formula.

Wherein R ′ ^b represents a carboxyl protecting group, L ² represents a halogen atom, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , A and Z Has the same meaning as above.)

Chi words, compound (Q) Ha B gain down compounds R ^'b to compound (P) - obtained Tsu by the and this is reacted with L ^2. Use here Examples of the solvent to be used include aromatic hydrocarbons such as benzene and toluene; halogens such as methylene chloride and chloroform. Non-protic polar solvents such as dimethyl hydrocarbon amide and dimethyl sulfoxide; and inert solvents such as acetate and nitrile. You can do it. The reaction temperature is usually from room temperature to about 10 ° C. This reaction is performed with tri-tinoleamine, diisopropinoletinoleamine, dicyclohexylamine, DBU, sodium carbonate, potassium carbonate, It is preferable to carry out the reaction in the presence of a basic compound such as sodium hydroxide.

 In the case where an amino group, imino group, hydroxy group, melcapto group, carboxyl group, etc., which are not involved in this reaction, are present in the starting compounds used in the above steps 1 to 3 However, these groups may be used in a protected form, and after completion of the reaction, the protecting group may be removed by a conventional method. The protecting group may be any one that can be removed without destroying the structure of the compound of the present invention formed by the reaction, and may be a peptide, an amino group, or the like. Groups commonly used in the field of sugar and nucleic acid chemistry are used.

 The starting compound (A) is produced by the method described in the following literature or a method analogous thereto.

 1) J. Het e roc y c l i c C he m. 22, 103 (1985)

 2) L i e b igs A n n .C he m. 2 9 (1 9 8 7)

3) 9 9 1 (1 9 8 8)

4) J. Org.Chem. 35, 930 (1970) 5) Japanese Patent Application Laid-Open No. Sho 62-2-464 541

 6) JP-A-62-262272

 7) Japanese Patent Application Laid-Open No. Sho 63-14545268

 8) J.Med.Chem.29, 2363 (1986) 9) J.F1uorinChem.28, 361 (1985)

10) JP-A-63-1969864

 1 1) Japanese Patent Application Laid-Open No. Sho 63-2646461

 1 2) Japanese Patent Application Laid-Open No. Sho 63-3-1049974

 1 3) European Patent Application No. 2300948

 1 4) Japanese Patent Application Laid-Open No. Hei 2 — 2 82 3 8 4

 1 5) Tokiohei 3-50 2 4 52

 17) J. Het. Chem. 27, 1609 (1990) The compound of the present invention thus obtained is isolated and purified according to a conventional method. Depending on the conditions of isolation and purification, it can be obtained in the form of a salt, free carboxylic acid or free amide, which can be converted into each other as desired to obtain the desired form. The compound of the present invention is produced.

 The compound (1) of the present invention or a salt thereof is a pharmaceutically acceptable carrier as an antibacterial agent for parenteral administration such as injection, rectal administration, ophthalmic administration and the like, or oral administration in solid or liquid form. A composition can be formulated with it.

Examples of the form of the antibacterial composition of the present invention for injection include pharmaceutically acceptable sterile water or non-aqueous solution, suspension and emulsion. Examples of suitable non-aqueous carriers, diluents, solvents or vehicles include propylene glycol, polyethylene, and the like. And glycols, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl ethyl oleate. Such compositions may also contain adjuvants, such as preserving, wetting, emulsifying, and dispersing agents. These compositions may be sterile solid compositions that can be dissolved, for example, by filtration through a bacteria-retaining filter, or immediately before use, in a sterilizing agent or some other sterile injectable medium. Bacteria can be sterilized by incorporating a sterilizing agent in the form described above.

 Formulations for ophthalmic administration may preferably contain, in addition to the present compound, a solubilizing agent, a preservative, an isotonic agent, a thickening agent and the like.

 Solid preparations for oral administration include capsules, tablets, pills, powders, and granules. In preparing these solid formulations, the compounds of the invention are generally mixed with at least one inert diluent, for example, sucrose, lactose or starch. This preparation may also use an additional substance other than the inert diluent, such as Hitoshi Nisawa (eg, magnesium stearate) in the usual formulation. In the case of capsules, tablets and pills, a buffer may be used. Tablets and pills may be provided with an enteric coating.

Liquid dosage forms for oral administration include inert diluents commonly used by those skilled in the art, for example, pharmaceutically acceptable emulsions, solutions, suspensions, syrups and emulsions, including water. Xylants. In addition to such inert diluents, the compositions may also contain adjuvants such as wetting agents, emulsifying, suspending, and sweetening, flavoring, and flavoring agents. Flavors can also be included. Formulations for rectal administration may preferably contain, in addition to the present compounds, excipients such as cocoa butter or a suppository box.

 The dose of the compound (1) of the present invention depends on the properties of the compound to be administered, the administration route, the desired treatment period and other factors, but is generally about 0.1 l / day for an adult. ~ 100 mg Z kg, especially about 0.5 ~: LOO mg Z kg is preferred. The daily dose can be divided into 2 to 4 divided doses, if desired.

 The compound (1) of the present invention and its salt have extremely high antibacterial effects and low phototoxicity and cytotoxicity, so that they can be used as pharmaceuticals for humans and animals, as fish disease drugs, agricultural chemicals, food preservatives, etc. Can be widely used. Further, the compound of the present invention can be expected to have an antiviral activity, particularly an anti-HIV (human immunodeficiency virus) activity, and is considered to be effective in preventing or treating AIDS.

 Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not intended to be limited to these.

 (Reference Example 1)

 Echinole 7 — Black mouth 6 — Fnoreo mouth 1, 4, 4-dihydro-1-41 (2, 4, 6 — Trifluorophenyl) 1-1, 8 — Naphthyridine 1 — Carboxylate:

Methyl 2 — (2, 6 — dichloro 5 — phenolic) 1 3 — ethoxy clear 6.40 g of tonoleene solution 10 2, 4, 4 and 6 ml under ice-cooling 5 ml of a toluene solution of 1.39 ml of phosphorus was added dropwise, and the mixture was stirred at room temperature overnight. The solvent is distilled off, ethanol is added, the crystals are collected by filtration, washed with ethyl ether, and ethyl 2, 6-dichloro-5-phenolic nicotine is added. Inore 3-Trinole Noro Lenophila Mino Acrylate was obtained. This ethyl 2, 6 — dichloro mouth 1 5 — phenolic nicotine 3 — (2, 4, 6 — triphenyl noreno phenolic) To a solution of 2.0 g of N, N-dimethylformamide (9 ml) was added 0.63 g of potassium carbonate, and the mixture was stirred at room temperature for 90 minutes. The reaction solution was poured into ice water, and the precipitated solid was collected by filtration, washed with ethanol and getyl ether to obtain 1.38 g of the title compound.

Properties: colorless powder

Melting point: 1 5 8 — 1 6 0

¹ HNMR (CDC 1 a) δ;

 1.41 (t, J = 7Hz, 3H), 4.42 (q, J = 7Η, 2Η), 6.92-7.06 (m, 2Η), 8.48 (d, J = 11 Η, 1), 8.49 (s, 1)

 (Reference Example 2)

 No. 7 — Chromo 1 — (2 — Chromo 4 — Fluoro Mouth) 1 6 — Fluoro Mouth 1, 4 — Dihydro 14 1 1, 8 — Naphthyridine 1 3 — Power box box rate:

 The title compound was obtained in the same manner as in Reference Example 1 except for using 2-chloro-4-phenololeaniline.

Properties: colorless powder Melting point: 1 7 7-1 7 8 ° C

 1 HNMRR (CDC1a) δ;

 1.41 (t, J = 7Hz, 3H), 4.41 (q, J = 7Hz, 2H), 7.23 (dd, J = 3Hz, 8Hz) , 1 H), 7.36-7.5 1 (m, 2 H),

8.49 (d, J = 7 Hz, 1 H), 8.49 (s, 1 H)

 (Reference Example 3)

 Echinore 11 (2—Chloro 4-Frönöröfönönöre) 1 6,7—Gifnoreo Mouth 1, 1—4—Jhidro 41 Line 3 — Power Box Rate:

Etinole 2 — (2, 4, 5 — Trifnoreo benzol) 13 — Ethoxy acrylate 2.46 g of a solution of chlorophonolem 13 Under ice-cooling, 5 ml of a solution of 1.2 ml of 2-chloro-4-anilineline was added dropwise to the ml under ice cooling, and the mixture was stirred at room temperature overnight. The solvent is distilled off, ethanol is added, and the crystals are collected by filtration, washed with ethyl ether, and then washed with ethyl alcohol 2 — (2, 4, 5 — trifluorobenzoyl). Nore) 1 3 — (2-Chloro 41) (Finorelo Fennino Amino) A clear rate was obtained. This technology 2 — (2,4,5 — Trinole ore benzoinole) 1 3 — (2 — Chloro 4-Folenoreo Lofeninorea Mino) 1.03 g of potassium carbonate was added to 15 g of a 3.0 g of N, N-dimethylformamide solution, and the mixture was stirred at room temperature for 90 minutes. The reaction solution was poured into ice water, and the precipitated solid was collected by filtration, washed with ethanol and diethyl ether to obtain 2.74 g of the title compound. Properties: Colorless scaly crystals

Melting point: 220 ° C (decomposition)

¹ HNMR (CDC 1 a) δ;

 1.40 (t, J = 7Hz, 3H), 4.39 (q, J = 7 J, 2Η), 6.54 (dd, J = 6Η,

1 1 Η,, 1 Η), 7.46 (d d, J = 3 Η ζ,

7 Η ζ, 1 Η), 7.56 (d d, J = 5 Hz, 9 Η ζ,

1Η), 7.50 — 7.64 (m, 2Η), 8.25-1 8.38 (m, 1Η), 8.34 (s, 1Η) [Reference Example 4 ]

 No. 7 — Black 1 (4 — Black 1 2 — Black hole 2) — 6 — Black 1 and 4 — 4 × 4 Saw 1, 8 — Naphthyridine 1 3 — Force box rate:

 The title compound was obtained in the same manner as in Reference Example 1 except that 4-chloro-2-aniline was used.

Properties: colorless powder

Melting point: 2 16-2 18 ° C

¹ HNMR (CDC 13) δ;

 1.41 (t, J = 7Η, 3Η) 4.40 (q, J = 7Hz, 2Η), 7.34-7.45 (m, 3H)

8.47 (d, J = 9 Η Η, 1 Η) 8.55 (s, 1 Η)

 (Reference Example 5)

Technology 7 — Chromo 6 — Fluoro 1 — (4 — Fluoro 2 — Methyl phenyl) 1, 4 — Dihydro 4 — Oki Saw 1, 8 — Naphthyridine 1 3 — Force box rate:

The title compound was obtained in the same manner as in Reference Example 1 except that 4-fluoro-2-methynoleaniline was used.

Properties: colorless powder

Melting point: 1 9 9 — 2 0 0

¹ HNMR (CDC 1 a) δ;

 1.40 (t, J = 7Hz, 3H), 2.06 (s, 3 3), 4.41 (q, J = 7Η, 2Η), 7.05- 7.17 (m, 2 Η), 7.2 3 (d, J = 5 Η, 1 J), 8.48 (d, J = 7 Η, 1 Η), 8.5 1 ( s, 1 Η)

 (Example 1)

Technology 7 — Chromo 1 — (2,4-Diphenyle 5 — Nitrofe 2) 1 6 — Phoro 1 1, 4-Dihydro 1 4 — ォKiso 1, 8 — Naphthyridine 1 3 — Force Revolving rate: Echino 7 — Chlor 1 — (2, 4 — Gifnooren) 1 6 — Phenoleuro 4 — Oxo 1, 4 --Hydroxy 1, 8 — Naphthyridine 1 3 —Carboxylate 2.0 g of 8 ml concentrated sulfuric acid Then, while stirring under ice-cooling, 600 mg of lithium nitrate was added little by little. The mixture was stirred at room temperature for 30 minutes to complete the nitration, and then the reaction solution was poured into 150 ml of a clog form and 100 ml of ice water while stirring. After stirring for minutes, liquid separation was performed, and the mouth layer layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The precipitated crystals are dispersed in ethanol and collected by filtration.Then, ethanol and diisopropyl ether are washed in this order. Thus, 2.08 g of the title compound was obtained.

Properties: colorless needle crystals

 Melting point: 2 5 6-25 7 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.41 (t, J = 7Η3H), 4.42 (d, J = 7Η, 1Η), 7.37 (t, J = 9Hz, 1Η), 8.35 (t, J = 7Η, 1Η), 8.49 (d, J = 7Η, 1Η), 8.54 (s, 1Η) [Example 2]

 7 — Black mouth _ 6 — Phenorero 1-11 (2, 4 — Dihnoreo mouth 1 5 — Nitroh fue 2 Nore) 1 1,4-Dihydro 1 4 — Oxo — 1, 8 — Naphthyridine 1 3 — Force oleonic acid:

 7-Chromo 1-(2, 4-diphenyl) 1-4-oxo 1, 4-dihydro 1, 8-naph Thiolidine — 3 — acetic acid 6.0 g was added to 25 ml of concentrated sulfuric acid, and 5.0 g of nitric acid rim was added little by little while stirring under ice-cooling. . The temperature was gradually raised and the mixture was stirred at 80 ° C for 2 hours. The mixture was allowed to cool, added to 200 g of ice water, and left overnight. The precipitate was collected by filtration, washed with distilled water, ethanol, and diisopropyl ether, and then air-dried to obtain 6.4 g of the title compound.

Properties: colorless powder

Melting point: 262-265 ° C (decomposition)

 1 HNMR (CDC13) δ;

8.15 (t, J = 11 Hz, 1H), 8.79 (d, J = 7Hz, 1H), 8.86 (t, J = 8Hz, 1 H), 9.17 (s, 1 H)

 (Example 3)

 1-(2, 4-difluoro 1-5-dihydro) 1-6, 7-difluoro-1, 4-dihydro 1-4 No. 3 — Power of boronic acid:

 1-(2, 4 — diphenyl phenol) 1, 6, 7-diphenyl 1, 4-dihydro 1 4 1 oxo 1 quinoline 1 3 — power 4 g of sulfonic acid was added to 40 ml of concentrated sulfuric acid, and 3.6 mg of potassium nitrate was added little by little, followed by stirring at room temperature for 1 hour. The reaction solution was poured into ice water and stirred overnight. The precipitated solid was collected by filtration and washed with water, ethanol and ethyl ether. 4.2 g of the title compound were obtained.

Properties: light yellow powder

Melting point:> 270 ° C

¹ HNMR (CDC 13) δ;

 7.70 (d d, J = 6Hz, 12Hz, 1H),

8.2 1 (t, J = 11Hz, 1H), 8.36 (t, J = 9Hz, 1H), 8.93 (t, J = 8Hz, 1H ), 9.10 (s, 1 H)

 (Example 4)

 Echinore 11 (2, 4 — diphenyl) 5 — 2-nitrophenyl 16 — 7, 7 — diphenyl 1, 4, 4 — dihydro 4 — oxo 1 quinolin 1 3 — card box rate:

1 — (2, 4 — difluoro 5 — dinitro) 1 6, 7 — difluoro 1, 4 — dihydro 1 4 — oxoquinoline To a solution of 4.2 g of phenolic acid was added 40 ml of dichloroethane, and 7 g of oxalyl chloride was added dropwise under ice-cooling. After completion of the dropwise addition, the mixture was stirred at room temperature for 2 hours. To this reaction solution, 15 ml of ethanol was added dropwise, and the mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, ethanol was added to the residue, the solid was collected by filtration, and the solid was washed with ethyl ether. 3.7 g of the title compound were obtained.

Properties: light yellow powder

Melting point: 1 6 5 — 1 7 3

'HNMR (d ₆ — DMSO) δ;

 2.74 (t, J = 7Hz, 3H), 4.37 (q,

J = 7 Hz, 2 H), 7.47 (dd, J = 10 Hz, 11 Hz, 1 H), 8.11-8.24 (m, 2H), 8 . 7 2 (s, 1 H), 8.93 (t, J = 9 Hz, 1 H)

 (Example 5)

 1 1 (2,4-diphenyl-5-nitrophenyl) 1,6,7,8—trifluor-1,4-dihydro-14-oxo Quinolin 1 3 — Force oleonic acid:

1 — (2, 4 — diphenyl olefin) 1 6, 7, 8 — trif noreo 1, 4-dihydro 4 — oxo 1 quinoline 1 1.7 g of 3-carboxylic acid was added to 10 ml of concentrated sulfuric acid, and 1.5 g of nitric acid was added little by little, and the mixture was heated and stirred at 60 ° C for a while. After allowing to cool, the mixture was poured into ice water and stirred overnight. The precipitated solid was collected by filtration and washed with water, ethanol, and getyl ether. 1.7 g of the title compound were obtained. Properties: light yellow powder

 Melting point: 2 4 5 — 25 5 ° C

'HNMR (d ₆ -DMS 0) δ;

 8.17 (t, J = 10Hz, 1H), 8.26 (t, J = 9Hz, 1H), 8.97 (s, 1H), 9.

0 0 (t, J = 8 Hz, 1 H)

 (Example 6)

 Echinore 1 — (2, 4 — Difluoro 1 5 — Nitrophenyl) 1 6, 7, 8 — Trif Norre 1 1, 4 — Dihydro 4 — OKI LINE LINE 3 — Power box:

 1 — (2, 4 — Difluoro 5 — Nitrophenyl) 1, 6, 7, 8 — Trifnoreo 1, 4 — Dihydro 1 4 — Oxo The title compound was obtained in the same manner as in Example 4 except that the use of norrin-3-3-carboxylic acid was carried out.

Properties: colorless powder

Melting point: 2 1 0-2 1 7

1 HNMR (d ₆ — DMSO) δ;

 1.27 (t, J = 7Η, 3Η), 4.26 (q, J = 7Η, 2Η), 8.07 (t, J = 11 1, 1 1) ), 8.16 (t, J = 10 Hz, 1Η), 8.

6 4 (s, 1H), 9.00 (t, J = 8Hz, 1H) (Example 7)

7 — Black mouth 6 — Phoreno 1, 4 — Dihydro 1 4 — Oxor 1 1 (2, 3, 4 1 Trif nore 5 — 2 Trof 1 1, 8 — Naphthyridine 1 3 — Power 7 — Black mouth 6 — Fuzoreo mouth 1, 4 --Hydroxy 1 --4oxo 1 — (2,3,4 1 -Trifluoro feninole) 1 1, 8- Naphthyridin-3-carbonic acid (890 mg) was added to concentrated sulfuric acid (10 ml), and potassium nitrate (730 mg) was added little by little, followed by stirring at room temperature for 2 days. After allowing to cool, the mixture was poured into ice water and stirred overnight. The precipitated solid was collected by filtration and washed with water, ethanol, and ethyl ether. 86 O mg of the title compound were obtained.

Properties: yellow powder

 ί point: 2 16-22 1 ° C

¹ HNMR (d ₆ — DMSO) δ;

 8.7 2 -8.84 (m, 2H), 9.1 1 (s, 1H)

 (Example 8)

 Echinore 7 — Krollo 6 — Phonore 1, 4 — Dihydro 1 4 1oxo 1 1 — (2, 3, 4 1 Trifnore 1 5 — 2 Tro 1, 8 — naphthyridine 1 3 — carboxylate:

 7 — Chromo 6 — Pheno Leo 1, 4-Hydro 1 4 — Oxo 11 (2, 3, 4 1) Trif nore Lo 5 — Nitro feni L) -1,8-Naphthyridin-13- The title compound was obtained in the same manner as in Example 4 except that carboxylic acid was used.

 1 HNMR (CDC13) δ;

1.41 (t, J = 7Hz, 3H), 4.42 (q, J = 7Η, 2Η), 8.18-8.26 (m, 1Η), 8.5 5 (d, J = 8 Η,, 1 Η), 8.5 4 (s, 1H)

 (Example 9)

 6, 7 — dihydro 1, 4 — dihydro 4 — oxo 1 1-(2, 3, 4 — trif noreo 5 — 2 trof 2) 1-quinoline 3-carboxylic acid:

 6, 7 — difluoro 1, 4-dihydro 4-oxo 1-1 (2, 3, 4-1 trifluorene) 1 quinoline 1 83-Omg of 3-carboxylic acid was added to 1Om1 of concentrated sulfuric acid, and 710mg of potassium nitrate was added little by little, followed by stirring at 100 ° C for 3 days. After allowing to cool, the mixture was poured into ice water and stirred overnight. The precipitated solid was collected by filtration and washed with water, ethanol, and getyl ether. 700 mg of the title compound were obtained.

Properties: light yellow powder

Melting point:> 2 15 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

 7.76 (dd, J = 6Hz, 11Hz, 1H), 8.37 (t, J = 9Hz, 1H), 8.85 (t, J = 6H z, 1H), 9.07 (s, 1H) [Example 10]

 Technology 6, 7 — Diphenol 1, 4 — Dihydro 4 — Oxo 1 11 (2, 3, 4 — Trifluorene 5 — Nitrofeny 1) 1 一 キ — — 3 力 3 力 力:

6, 7 — diphnole mouth 1, 4-dihydro 4 1 year old kiso 11 (2, 3, 4-trifnorole 5-nitrofenyl) Monoquinoline — 3 — The use of carboxylic acid was the same as in Example 4. Thus, the title compound was obtained.

Properties: colorless powder

Melting point: 10 6 — 1 15 ° C

 'H NMR (CDC13) δ;

 1.2 7 (t, J = 7 Hz, 3 H), 4.24 (q,

J = 7Hz, 2H), 7.53 (dd, J = 6Hz, 11Hz, 1H), 8.16 (t, J = 10Hz, 1H), 8.69 (s, 1H), 8.83 (t, J = 8Hz, 1H)

 (Example 11)

 Echinore 7 — Black mouth 1 6 — Fenoole 1, 4 — Dihydro 1 4 — Oxo 1 1 — (2, 4, 6 — Trifnoreo mouth 13 — 2 Mouth fermentation)-1, 8-Naphthyridine 1-3-Carboxylate:

 Echinore 7 — Black mouth 1 6 — Phenorero 1, 4 — Dihydro 1 4 — Oxo 1 1 1 (2, 4, 6 — Trifluorene) 1 1 The title compound was obtained in the same manner as in Example 1 except that naphthyridine-13-potassium oleate was used.

Properties: yellow powder

Melting point: 1 7 7-18 4 ° C

 • HNMRR (CDC13) δ;

1.42 (t, J = 7Hz, 3H), 4.43 (q, J = 7Hz, 2H), 7.24 (t, J = 11Hz, 2H) ), 8.49 (s, 1H), 8.50 (d, J = 10Hz, 1H) (Example 12)

 7 7-Black mouth 1-(2-Black mouth 4-4

-5-2-fluoro-2) 1-6-Fluoro 1, 4-Dihydro 4-1-1, 8-Naphthyridine 1-3-Carboki The format:

 Technology 7 — Black mouth 1 1 1 (2 — Black mouth 1 4 1 Fluoro 2 1) 1 6 — Fluoro 1, 4 — Dihydro 4 oxo The title compound was obtained in the same manner as in Example 1 except that 1,8-naphthyridine-1-3-carboxylate was used.

 Properties: colorless needle crystals

 Melting point: 2 3 7 — 2 42 ° C (decomposition)

 1 HNMR (CDC13) δ;

 1.41 (t, J = 7Hz, 3H), 4.40 (q, J = 7Η, 2Η), 7.62 (d, J = 10 0, 1 1) ), 8.19 (d, J = 8 Hz, 1 H), 8.

50 (d, J = 8Hz, 1H), 8.55 (s, 1H) [Example 13]

 Ethyl 11 (2—Chloro 4—Finoleo 5—Nitrofe 2 Nore) 1-6, 7—Gifnole 1-1,4—Dihydro 4— KIKI KINO LIN LINE 3 — Carboxylate:

 1-1 (2-1-1 mouth) 4-6, 7-1-4-, 1-4-1-4-4 The title compound was obtained in the same manner as in Example 1 except for using a non-reactive boxrate.

Properties: Pale yellow needle crystals Melting point: 2 16-2 19 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.41 (t, J = 7Hz, 3H), 4.40 (q, J = 7Hz, 2H), 6.53 (dd, J = 6Hz, 12H z, 1 H), 7.77 (d, J = ll H z,

1H), 8.32 (s, 1H), 8.26-8.35 (m, 1H), 8.40 (d, J = 7Hz, 1H) (Example 14 〕

 7 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 0 1, 4-Dihydro -4-Oxo 1, 8-Naphthyridine 1 3-Force box:

 No. 7-Black 1-4 (1-2-Black 2) 6-6-1, 4-1-4 1, 8—Naphthyridine 1 3 —force The title compound was obtained in the same manner as in Example 1 except for using carboxylic acid.

Properties: colorless needle crystals

Melting point: 2 19-22 1 ° C

 'H NMR (CDC13) δ;

 1.41 (t, J = 7 Hz, 3 H), 4.40 (q,

J = 7Hz, 2H), 7.62 (d, J = 10Hz, 1H), 8.19 (d, J = 8Hz, 1H), 8.50 ( d, J = 8 Hz, 1 H), 8.55 (s, 1 H) [Example 15]

Technology 7 — Black mouth 6 — Funoleo 1 — (4 — Funoleo Mouth 1 2 — Methinole 5 — Two trophone 2 1 1, 4 1 Dihydro 4 1 Oxo 1 1, 8 — Naphthyridine 1 3 — Power X-Rate:

 Technology 7 — Chromo 6 — Pheno Leo 1 — (4-Fo No Le 2) — 1, 4 — Dihydro 4 — Oxo 1 The title compound was obtained in the same manner as in Example 1 except for using 1,8-naphthyridine-13-potassium benzoate.

Properties: colorless powder

Melting point: 2 15-2 16 ° C

 'H NMR (CDC1a) δ;

 1.41 (t, J = 7 7, 3Η), 2.19 (s, 1Η), 4.43 (q, J = 7Η, 2Η), 7.41 ( d, J = 8 Η 1, 1 Η), 8. 1 1 (d, J = 7 1 1, 1 Η), 8.50 (s, 1 Η), 8.5 2 (d, J = 8 Η Η ζ, 1 Η)

 (Example 16)

1 1 (3-Amino 4, 6-Difluorene) 1 7-Black 1-6-1-4-1-4 Oxo 1, 8 — Naphthyridine 1 3 — Power No. Revolving: Etino 7 — Black 1 6 — Noro 1 1 ((2,4)ー 5 二 口 口 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1. Of 0 g with 280 mg of 10% palladium carbon, 50 ml of dichloromethane, 30 ml of ethanol and 2 ml of concentrated hydrochloric acid. The mixture was added and hydrogenated at room temperature overnight. Pyridine 2 ml was added, and the mixture was concentrated under reduced pressure. To the residue was added 80 ml of porcine mouth water and 10 ml of distilled water, and the layers were separated.The porosity home layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the residue was added 8 ml of ethanol, and the mixture was allowed to stand at room temperature. The precipitate was collected by filtration, washed with ethanol, and then washed with diisopropanolone ether in order. 95 g of the title compound were obtained.

Properties: colorless powder

 ίpoint: 2 0 8 — 210 ° C

'HNMR (d ₆ — DMSO) δ;

 1.27 (t, J = 7 Hz, 3 H), 4.24 (q,

J = 7Hz, 2H), 7.11 (t, J = 8Hz, 1H), 7.47 (t, J = 10Hz, 1H), 8.53 ( d, J = 8 Hz, 1 H), 8.71 (s, 1 H) (Example 17)

 1 1 (3—Amino 4 and 6—Di-Finorelo-Feninore) 1 7 1 Black mouth 1 6—Funoleo 1 and 4—Dihydro 1 4—Oxo 1 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 Echinore 11 (3—Amino 1, 4, 6—Difluorophenyl) 1 7—Black mouth 6—Funoleo mouth 1, 4, 4-Dihydro 4 To 0.6 g of oxo-1,8-naphthyridine-13-potassium oxylate was added 4 ml of a mixture of 3N hydrochloric acid / monoacetic acid, and the mixture was heated under reflux for 2 hours. After adding 3 ml of distilled water and refluxing for 5 minutes, the precipitate was collected and washed with ethanol to obtain 0.54 g of the title compound.

Properties: yellow powder Melting point:〉 270 ° C

_{1 HNMR (d 6 - DMSO)} δ;

 5.46 (s, 2H), 7.00 (t, J = 8Hz, 1H), 7.43 (t, J = 10Hz, 1H), 8.76 (d, J = 8 Hz, 1 H), 8.97 (s, 1 H)

(Example 18)

 1 1 (3—amino 4, 6—diphenyl phenyl) 1-6, 7—diphenyl 1, 4—dihydro 4—oxo One quinoline one 3 — Power box box rate:

 Echinore 11 (2, 4 — diphenyl phenol 5 — nitric oxide phenol) 1 6, 7 — diphenyl phenol 1, 4 — dihydro 1 4 — oxo 3.7 g of quinolin-3-carboxylate was dissolved in 60 ml of acetic acid, and 400 mg of 10% paradium carbon was added. The mixture was stirred at room temperature under a hydrogen atmosphere for 2 days. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 2.

9 g of the title compound were obtained.

Properties: yellow powder

Melting point: 1 98-205 ° C

] HNMR (d ₆ -DMSO) δ;

1.28 (t, J = 7Hz, 3H), 4.23 (q, J = 7Hz, 2H), 5.52 (s, 2H), 7.01 ( t, J = 9 Hz, 1 H), 7.19 (dd, J = 6 Hz, 10 Hz, 1 H), 8.14 (t, J = 9 Hz, 1 H) , 8.5 4 (s, 1 H) (Example 19)

 1 1 (3-amino 4, 6-diphenyl phenyl) 1 6, 7-diphenyl 1, 4-dihydro 4-oxoquinolineー 3 — carboxylic acid:

 Technology 1 (3—Amino 4, 6—Gifnole Lofeninole) 1 6, 7—Gifnole 1,4—Dihydro 4—Oxo 1 g of monoquinoline 13-potassium oxylate was added to 8 ml of acetic acid and 2 ml of hydrochloric acid, and the mixture was refluxed overnight. After cooling, the reaction solution was concentrated under reduced pressure, ethanol was added to the residue, and the solid was collected by filtration and washed with diethyl ether. 83 O mg of the title compound were obtained.

Properties: colorless powder

Melting point:> 270 ° C

 'H N M R (d-D M S 0) δ;

 7.14 (t, J = 9Hz, 1H), 7.47 (dd, J = 6Hz, 10Hz, 1H), 7.54 (t, J = 10 Hz, 1H), 8.34 (t, J = 10Hz, 1H), 8.89 (s, 1H)

 (Example 20)

 Echinore 11 (3—Amino 4, 6—Diphenylolenophenyl) 1,6,7,8—Trif Noreo Mouth 1,4—Dihydro 1 4—O KIRO KI LIN LINE 1 3 — Power BOX:

Echinore 11 (2, 4 — diphenyleol 5 — dinitrophenyl) 1, 6, 7, 8 — Trifolenorex 1, 4 — dihydro 41 Kiso-kinolin 3-Power box box 2.2 g It was dissolved in evening water (20 ml), acetic acid (50 ml) and dichloroethane (10 ml), and 100% palladium carbon (200 mg) was added. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 1.12 g of the title compound were obtained.

 Properties: yellow powder

 Melting point: 1 87-196 ° C

'HNMR (d ₆ -DMS 0) δ;

 1.28 (t, J = 7 7, 3Η), 4.22 (q, J = 7Η, 2Η), 5.49 (s, 2Η), 7.11 ( t, J = 8 Η 1, 1 Η), 7.42 (t, J = 10 Η, 1 Η), 8.05 (t, J = 10 Η ζ, 1 Η), 8. 4 6 (s, 1 Η)

 (Example 21)

 1-(3-Amino 4, 6-difluorophenyl) 1-6, 7, 8-Trifnorole 1-4, 4-Hydro 1-4 Norrin 1-force oleonic acid:

 Echinore 11 (3—Amino 1-4, 6—Difluorophenyl) 1, 6, 7, 8—Trif Noreo Mouth 1, 4—Dihydro 1 41 The title compound was obtained in the same manner as in Example 19, except that quinoline-3—carboxylate was used.

Properties: colorless powder

Melting point: 25 6-26 1 ° C

'HNMR (dDMSO) δ; 7.15-7.30 (m, 1H), 7.49 (t, J = 10Hz, 1H), 8.25 (t, J = 8Hz, 1H) , 8.77 (s, 1 H)

 [Example 22]

 No. 1 — (3—Amino 4,5,6—Tri-no-re-open mouth) 1 7—Kuro-no-one 6—Fonore-ro 1,4—Dihydroー 4 1 oxo 1, 8 — naphthyridine 1 3 — carboxylate:

 Echinore 7 — Black mouth 6 — Phenole 1, 4 — Dihydro 1 — 1oxo 1 1 — (2, 3, 4 — Trif nore 5 — 2 Tro 1,8-Naphthyridine 13-Dissolve 80 mg of carboxylic acid in 80 ml of methanol and 1 ml of acetic acid. % Palladium carbon 8 O mg was added. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Ethanol was added to the residue, and the solid was collected by filtration and washed with diethyl ether. 200 mg of the title compound were obtained.

Properties: brown powder

Melting point: 16.5-17.4 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.2 9 (t, J = 7 Η, 3), 4.26 (q, J = 7 Η, 2), 5.8 2 (s, 2), 8.5 5 ( d, J = 8Η Η, 1ζ), 8.75 (s, 1 ，) [Example 23]

1 I (3—Amino I, 4, 5, 6—Trif Noreo Lo Feninore) — 7 — chloro 6 — phenol 1, 4 — dihydro 1 4 — oxo 1, 8 — naphthyridine 1 3 — carboxylic acid:

 Ethyl 1-(3-Amino 4, 5, 6-Trifluorophenyl)-1-7-Chloro 6-Fluoro 1, 4-Dihydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Powerboxylate 600 mg in 30 ml of methanol, 10 ml of acetic acid, dichloroethane It was dissolved in 30 ml and 100 mg of 100% palladium carbon was added. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Acetic acid (4 ml) and hydrochloric acid (1 ml) were added to the residue, and the mixture was heated and stirred at 100 ° C at room temperature. The reaction solution was concentrated under reduced pressure, getyl ether was added to the residue, and the solid was collected by filtration and washed with getyl ether. 16 O mg of the title compound were obtained.

Properties: light yellow powder

Melting point:〉 24 2 ° C (decomposition)

_{^{1 HNMR (d s - DMSO)}} δ;

 6.87 (t, J = 5Hz, 1H), 7.76 (d, J = 8 8, 1Η), 9.02 (s1H) [Example 24]

 Echinore 11 (3—Amino 4, 5, 6—Triphenylamine mouth phenyl) 1-6, 7—Diphenyle 1,4—Dihydro 1 41 Okisokinori 3-Power box rate:

Technology 6, 7 — difluoro 1, 4-dihydro 4 — oxo 1 11 (2, 3, 4 — trif nore ro 5 — 2 trofeni Nore) 1 quinoline 1 3 — carboxylate 2 8 O mg It was dissolved in 10 ml of ethanol, 5 ml of acetic acid and 5 ml of dichloromethane, and 30 mg of 10% palladium carbon was added. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 200 mg of the title compound were obtained.

Properties: yellow powder

Melting point: 1 16-124 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 1.22 (t, J = 7 Hz, 3 H), 4.2 2 (q,

J = 7 Hz, 2 H), 5.85 (s 2 H), 6.

8 3 (t, J = 8 Hz, 1 H), 7 4 2 (d d,

J = 6 H z, 1 2 H z, 1 H), 8 1 3 (t, J

= 10 Hz, 1 H), 8.60 (s 1 H) (Example 25)

 1 — (3-Amino 4, 5 6 — Trif Norole vinyl) 1 6, 7 — Gif 1 4 Quinolin 1 3 — carboxylic acid:

 Technology 1 — (3—Amino 4,5,6—Tri-Finole opening) 1-6,7—Difluoro 1,4—Dihydro 1— The title compound was obtained in the same manner as in Example 23 except that oxoquinoline-13-potassium oxalate was used.

Properties: light yellow powder

Melting point:〉 2 11 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ; 5.91 (brs, 2H), 6.86 (t, J = 7Hz, 1H), 7.68 (dd, J = 7Hz, 11Hz, 1H), 8.3.4 (t, J = 9Hz, 1H), 8.94 (s, 1H)

 (Example 26)

 Echinore 1 — (3—Amino 1, 2, 4, 6 — Tri-Fenole mouth, phenyl) 1-Cro mouth 16 — Fenoole 1, 4, 4 — 'Low 4 1-1, 1-8-Naphthyridine 1-3-

 Ethyl 1 — (2,4,6 — Trinole 3-Nitroguchi 1 2)-7-Black 1-6- The title compound was obtained in the same manner as in Example 16 except that oxobox 1,8, -naphthyridine-13-potassoleboxylate was used.

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7 Hz, 3 H), 4.40 (q, J = 7 Η, 2), 6.8 3 — 7.0 4 4 (br, 2), 7.22-7.35 (m, 1Η), 8.48 (d, J = 8Η, 1Η), 8.50 (s, 1Η) [Example 27]

 1-(3-Amino 2, 4, 6-Trif Norre Lo Fennino)-7-Chlo Lo 6-Phreno Lo 1, 4-Dihydro 1 4- Kiso 1, 8 — naphthyridine 1 3 — carboxylic acid:

1 1 (3—Amino 2,4,6—Tri-no-leo mouth) 2 7—Kuro-ro 6—Hu-no-le 1--4 (B) 4-oxo-11,8-naphthyridine-13-force The title compound was obtained in the same manner as in Example 17 except that oleboxylate was used.

 Properties: light yellow powder

 Melting point: 2 22-2 28 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 7.44 (t, J = 11 Hz, 1H), 8.77 (d, J = 8Hz, 1H), 9.21 (s, 1H) [Example 28 ]

 1 1 3 3 3 3 3 3 — 1 3 3 3 3 1 7 7 7 ク 1 — — 4 — Oxo 1, 8 — Naphthyridine 1 3 — Power box:

 Echinore 1 1 (6—Chloro 4—Funoleo 1—3—Nitro 2 1) 7—Kuro 1 6—Fonole 1 1 4—Jihdro 4 —Oxo-1,8—Naphthyridine-13—The title compound was obtained in the same manner as in Example 16 except that carboxylate was used.

Properties: yellow powder

Melting point: 206-208 ° C

¹ HNMR (CDC 13) δ;

1.41 (t, J = 7Η, 3Η), 4.40 (q, J = 7Η, 2Η), 6.86 (d, J = 8Η, 1Η) , 7.26 (d, J = 1 1 Η ζ, 1 Η), 8.48 (d, J = 8 Η ζ, 1 Η), 8.49 (s, 1 Η) (Example 29)

 1 1 (3—Amino 6—Black mouth 4—Fournole lophenyl) — 7—Cro mouth 1 6—Funoleo mouth 1, 4—Hydrogen 4 1 year old key Saw 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 No. 11 (3—Amino 6—Chloro 4—Fnoleo phenyl) 1—7—Chloro 6—Funoleo 1, 4—Dihydro 4-oxo-11,8-naphthyridine-13-force The title compound was obtained in the same manner as in Example 17 except that oleboxylate was used.

Properties: light yellow powder

Melting point: 2 65-26 7 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 5.81 (s, 2), 7.07 (d, J = 8Hz, 1H), 7.52 (d, J = 11Hz, 1H), 8.76 (d, J = 7Hz, 1H), 8.93 (s, 1H)

 (Example 30)

 1 1 (3—Amino 6—Chloro 4—Funoleo Mouth) 1 6,7—Difnole Mouth 1,4—Jihydro 4 1 Oxo Ikinori I 3 — Carboxylate:

 Technology 1-(6-Fluoro 1-4 1 Fluoro 3-2 Tro 2) 1 6,7-Diph Nore 1, 4-Dihydro 1 4 1 The title compound was obtained in the same manner as in Example 16 except for the use of oxoquinoline-13-forceboxyl acrylate.

 1 HNMR (CDC13) δ;

1.39 (t, J = 7 Hz, 3 H), 4.38 (o, J = 7 Hz, 2 H), 6.65 (dd, J = 5 Hz, 12 Hz, 1 H), 6.91 (d, J = 9 Hz, 1 H), 7 3 1 (d, J = 11 Hz, 1 H), 8.28 (q, J = 9 Hz, 16 Hz, 1 H), 8.35 (s, 1 H) [ Example 31)

 1 — (3 — Amino 6-Chloro 4 — Phenorero Feninore) — 6, 7 — Gifnorero 1, 4 — Dihydro 1 4 — Oki Norin 1 3 — Power

 No. 11 (3—Amino 6—Cross 1—4—Normal) 1—6, 7—Difnole 1—4—Dihydro 4— The title compound was obtained in the same manner as in Example 19 except for using oxoquinolin-13-carboxylate.

Properties: colorless powder

Melting point:〉 270 ° C

1 HNMR (d ₆ -DMS 0) δ;

 5.91 (brs, 1H), 7.08 (d, J = 8Hz, 1H), 7.34 (dd, J = 7Hz, 11Hz, 1H), 7.59 (d, J = 12Hz, 1H), 8.35 (t, J = 11Hz, 1H), 8.83 (s, 1H)

 (Example 32)

No. 1 — (3 — Amino 4 — Black 1 6 — Black 1 6 7 — Black 6 — Black 6, 1 — 4 Mouth 4 1 oxo 1, 8 — naphthyridine 1 3 — force box rate: 1-(4-Black mouth 1-6-Fluoro 1-3-Nitro feninole) 1-7-Black mouth 1-6-Fluoro 1, 4-Dihydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Power The title compound was obtained in the same manner as in Example 16 except that oleboxylate was used.

 Properties: light yellow powder

 Melting point: 200-202 ° C

 1 HNMR (CDC13) δ;

 1.40 (t, J = 7Η, 3Η), 4.40 (q, J = 7Hz, 2Η), 6.8.2 (d, J = 7Hz,

1Η), 7.29 (d, J = 11 1, 1 1), 8.47 (d, J = 8Η, 1Η), 8.55 (s, 1Η) [ Example 33)

 1-(3-Amino 4-Black mouth 1-6-Holo Leno Ninore) 1 7-Chloro 6-Holo 1-4-Dihydro 1 4-Oki Saw 1, 8 — Naphthyridine 1 3 — Force oleic acid:

レ 1 — (3 (— (1 1 3 3 3 3 1 1 1 1 1 3 1 7 7 1 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Powerboxylate 1.0 g of acetic acid, 10 ml of acetic acid, 10 ml of methanol, 10 ml of dichloromethane After dissolving in 20 ml of tan, 13 mg of 10% paradium carbon suspended in 20 ml of acetic acid was added, and the mixture was stirred overnight under a hydrogen stream. The palladium carbon was filtered through a membrane filter, 10% sodium hydroxide was added to the filtrate, and the mixture was extracted with a black hole form. After drying the organic layer, the solvent is distilled off and the solid is filtered. A collection of 0.38 Og of the title compound was obtained.

Properties: light yellow powder

Melting point:〉 2 7 0

 'H N M R (de-D M S O) δ;

 5.76 (br, 2H), 7.03 (d, J = 9Hz, 1H), 7.57 (d, J = 10Hz, 1H), 8.78 (d, J = 8 Hz, 1 H), 9.00 (s, 1 H) (Example 34)

 Echinole 11 (3—Amino 14—Fonole 1) 2—Methylfour 2 1 7—Chloro 6—Fenole 1 1,4 1ー 4 — Oxo 1, 8 — Naphthyridine 1 3 — Carboxylate:

 1 1 (4 — Fluorine 2 — Methyl 1 3 — Nitro 2) 1 7 — Chromo 6 — Fluoro 1, 4 1 4—oxo 1, 8—naphthyridine 13 —force The title compound was obtained in the same manner as in Example 16 except that oleboxylate was used.

Properties: light yellow powder

Melting point: 2 1 2 — 2 13 ° C

 'H NMR (CDC13) δ;

 1.41 (t, J = 7 Η, 3), 1.9 1 (s,

3), 3.79-3.96 (br 2), 4.

4 0 (q, J = 7 Hz, 2 Η), 6 7 0 (d, J

= 8 Η,, 1 Η), 7.02 (d, J = 1 1 Η ζ,

1 Η), 8.50 (d, J = 1 1 Η,, 1 Η), 8. 5 0 (s, 1 H)

 (Example 35)

 1-(3-Amino 4-Fluoro 2-Methinolephenyl)-7-Chloro 6-Fluoro 1-1, 4-Dihydro 4-oxoー 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 Echinole 11 (3-Amino 14-Fenole 1-7-Methyl phenol 2) 1 7-Chloro 6-Fenole 1-4-Dihydro 4-oxo-11,8-naphthyridine-13-force The title compound was obtained in the same manner as in Example 17 except that oleboxylate was used.

Properties: colorless powder

Melting point: 2 7 4-27 9 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.8.4 (s, 3Η), 6.95 (d, J = 8Η, 1Η), 7.19 (d, J = 1 22, 1Η), 8.75 (d, J = 8Η, 1 1), 8.79 (s, 1Η) [Example 36]

No. 7 — Black mouth 1 — (2, 4 — Difluorene 5-Honoreminore aminohn 2) 1 — 6 — Holenorro 1, 4 Row 4 1, 1, 8 — Naphthyridine 1 3 — Force box:

No. 7 — Black mouth 6 — Fluoro 1-11 (2, 4 — Difnoreo mouth 5 — 2 Tropaninole) _ 4 — Oxo 1 1, 4 — J Hydro 1,8 —Naphthyridine 1 3 —Holeboxylate 3.5 g with 28 O mg of 10%, ⁰ % radiocarbon , The mixture was added to a mixture of 20 ml of dichloromethane, 10 ml of formic acid and 0.3 m] of concentrated hydrochloric acid, and hydrogenated at room temperature for 5 hours. 1. Add 2 ml of acetic anhydride, leave at room temperature for 1 hour, filter the catalyst, concentrate under reduced pressure, disperse the precipitate in ethanol, and filter. Nose, then wash in order, then wash

2.65 g of the title compound were obtained.

Properties: colorless powder

Melting point:〉 270

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.28 (t, J = 7 Hz, 3 H), 4.25 (q,

J = 7Hz, 2H), 7.77 (dd, J = 10Hz, 11Hz, 1H), 8.35 (s, 1H), 8.45 (t , J = 8Hz, 1H), 8.54 (d, J = 8Hz, 1H), 8.77 (s, 1H)

 (Example 37)

 7 — Chlorine 1 — (2, 4 — Dinoremo 5 — Honorémiorinoreminoru) _ 6 — Phorenoro 1, 4 — Dihidro 1 41 Oxo 1, 8 — Naphthyridine 1 3 — Power

1 1 (3—Amino 4 and 6—Gifanoleo phenyl) 1 7—Chloro 6—Fluoro 1 4 1-oxo 1 and 4-Dihydro— 1,8-Naphthyridine-13-force Norvonic acid 46.5 mg was dissolved in 1 ml of formic acid, 0.2 g of acetic anhydride was added, and the mixture was stirred at 60 ° C for 1 hour. The mixture was concentrated under reduced pressure, 2 ml of ethanol was added to the residue, and the mixture was stirred at 60 ° C for 2 hours. The precipitate was collected by filtration, washed with ethanol and diisopropynolate in that order, and then dried. The title compound was obtained.

 Properties: colorless powder

 Melting point:〉 270 ° C

 'H N M R (de-D M S O) δ;

 3.46 (brs, 1H), 778 (dd, J =

10 Hz, 11 Η 1, 1 H), 835 (s, 1H), 8.50 (t, J = 8Hz, 1H), 8.76 (d, J = 8Hz, 1H), 9.08 (s1H) (Example 38)

 Ethyl 7 — Chlorine 11 (2, 4 — Diphnoreo mouth 1 5 — Holmylmethine) Aminophane 2 1) 6 — Phenole mouth 1, 1, 4 Hydro 1 4 1 oxo 1, 8 — naphthyridine 1 3 — force boxyrate:

 No. 7 — Kuro mouth 1 1 1 (2, 4 — Gifnoreo Mouth 1 5 — Honore Mir Aminofen 2 1) 1 6 — Hunoleol 1, 4 — Jihydro -4 1-oxo-1,8-naphthyridine-13-canoleboxylate 500 mg of 500 mg of potassium carbonate, 1.5 g of sodium carbonate The mixture was mixed with 2.5 ml of N, N-dimethylhonolemamide together with methyl urea and stirred at 50 ° C for 1 hour. After adding 40 ml of chloroform and 150 ml of distilled water to separate the layers, the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The mixture was dispersed in ethanol, collected by filtration, and washed with ethanol and diisopropyl ether in that order to obtain 455 mg of the title compound. Properties: colorless crystals

Melting point: 26 4-26 7 ° C ¹ HNMR (CDC 13) δ;

 1.41 (t, J = 7Hz, 3H), 3.34 (s, 3H), 4.42 (q, J = 7Hz, 2H), 7.27 ( t, J = 10 Hz, 1 H), 7.39 (t, J = 7 Hz, 1 H), 8.35 (s, 1 H), 8.49 (d, J = 7 Hz, 1 H), 8.56 (s, 1 H) (Example 39)

 Echizore 1 — (3 — t — Butoxyl carbylamino 1, 2,4-difluorobenzene) 1 7 —Kuro 1-6 — oriole 1,4 Draw 4 — Oxo 1, 8 — Naphthyridine 1 3 — Carboxyrate:

N — (t—butanol) — 2,6 — difluoro — 3 —2 troaniline 2. O g in 0 ml of 20 ml of methanol Hydrogen was added using 2 g of 10% palladium carbon at room temperature for 3 days. After filtering off the catalyst, the filtrate is used as it is with 0.5 mm o 1 Z ml of ethyl alcohol 2 — (2'6 '-dichloro-opener 5-phenolic outlet nicotinol) 1 3 — Added ethoxylate acrylate to a solution of 20 ml of the dissolved dichloromethan. This solution was concentrated under reduced pressure. To the residue, 2.5 g of anhydrous sodium carbonate and 10 ml of N, N-dimethylformamide were added, and the mixture was added at 90 ° C for 30 minutes. Stirred. After allowing the mixture to cool, 100 1111 chloroform and 4001111 distilled water were added to separate the solution.Then, the mouth layer was washed twice with 400 ml of distilled water. After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure, 1 ml of ethanol was added, and the mixture was allowed to stand. The residue was chromatographed using 150 g of silica gel (solvent). Effluent, cross-port holm 1 cross-port holm: methanol no = 7.5: 1) Precipitate from fraction corresponding to the main product from ethanol is converted to ethanol. The dispersion was collected by filtration to obtain 575 mg of the title compound. Properties: colorless crystals

 Melting point: 1 2 8 — 13 1 ° C

¹ HNMR (CDC 13) δ;

 1.40 (t, J = 7Hz, 3rd), 1.51 (s, 9th), 4.40 (q, J = 7th, 2nd), 6.11 ( s, 1 Η), 7.16 (t, J = 11 Η, 1 Η), 7.30 (t, J = 7 Hz, 1 Η), 8.

4 8 (d, J = 7Hz, 1H), 8.54 (s, 1H) [Example 40]

 1 — (3 — Amino 2, 4-diphenyl phenol) 1 7 — Chlorine 6 — Phenolero 1, 4-Hydro 4 — Oxo — 1, 8 — naphthyridine 1 3 — force oleic acid:

No. 1 — (3 — t — Butoksika Norreboninolea Min. 1, 4 — Jif Norelo Lenil) 1 7 — Chloro 6 — Flou mouth 1, 4 — J Hydro 4 — Oxo 1, 8 — Naphthyridine 1 3 — Forced boxylate 50 Omg was added to 8 ml of a mixture of 3N hydrochloric acid and acetic acid. The mixture was stirred and refluxed for 5 hours. 16 ml of distilled water was added, the mixture was heated under reflux for 10 minutes, and then allowed to cool. 80 ml of clos- ing porosity and 10 ml of distilled water were added thereto to carry out liquid separation, and the croat-forming form layer was concentrated under reduced pressure. The precipitate was dispersed in ethanol and collected by filtration. The precipitate was washed with ethanol and diisopropyl ether in that order to give 295 mg of the title compound. Properties: yellow powder

 Melting point: 2 4 4-2 48 ° C (decomposition)

 1 HNMR (CDC13) δ;

 4.04 (s, 1Η), 6.64 (dt, J = 5Hz, 8Hz, 1H), 7.02 (dd, J = 2Hz,

8 Hz, 10 Hz, 1 H), 8.52 (d, J = 7 Hz, 1 H), 8.87 (s, 1 H)

 (Example 41)

 1 1 (3-Benzoi Nore Amino 1-4, 6-Gifnore Orofe 2 Nore) 1 7-Kuroguchi 1 6-Fluoro 1, 4-Jihidoro 4 — Oxo 1, 8 — Naphthyridine 1 3 — Force

1-(3-Amino 4, 6-Diphenyl phenol) 1 7-Black mouth 6-Phenole 4-Oxo 1, 4-Dihydro 1 1,8-Naphthyridine-l-3 -Rubonic acid 31 Omg together with 220 mg of benzoic anhydride to 920 mg of N, N-dimethylformamide In addition, the mixture was stirred at 70 ° C for 2 hours and at 100 ° C for 2.5 hours. Add 5 O ml of cross-linked porum and 15 O ml of distilled water to separate the layers. Dry the cross-linked porum layer with anhydrous magnesium sulfate and concentrate it under reduced pressure. Was added with 6 ml of ethanol, and the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order to obtain 184 mg of the title compound. .

Properties: light brown powder

Melting point: 260-26 3 ° C

_{'HNMR (d 6 - DMSO)} <5;

7.5 3-7.68 (m, 3H), 7.80 (t, J = 10 Hz, 1 H), 7.98 (d, J = 8 Hz, 2 H), 8.11 (t, J = 7 Hz, 1 H), 9.09 ( s, 1H), 10.0.4 (s, 1H) [Example 42]

 Technology 7 — Chlorine 1 — (2,4-Diphenylamine 5 — Methylamine Minophenyl) 1 — 6—Holeone Mouth 1, 4 — Dihydro 4 1 oxo 1, 8 — naphthyridine 1 3 — force

 1 1 (5—Amino 2, 4—Diphenylophenyl) 1 7—Chloro 6—Fluoro1 41 1oxo1 1, 4—Jihi Dro 1, 8 — Naphthyridine 1 3 — Forced Boxylate 500 mg with 100 mg of 37% formalin and 10 ml of 1, 2 — To a mixture of dichloroethane, 5 ml of methanol and 0.5 ml of acetic acid, and hydrogenated with 0.08 g of 10% paradium carbon (16 Time). After the catalyst was removed by filtration, the filtrate was concentrated under reduced pressure, the residue was dissolved in 50 ml of a cross-section hologram, washed with 5096 aqueous sodium carbonate solution, and then dried with anhydrous sulfuric acid. After drying with acid magnesium, it was concentrated under reduced pressure. The residue was subjected to chromatography using 20 g of silica gel (eluate, chloroform) to obtain 150 mg of the title compound.

Properties: pale yellow needles

Melting point: 2 26-23 1 ° C

 1 HNMR (CDC13) δ;

1.41 (t, J = 7 Hz, 3 H), 2.89 (s, 3 H), 4.41 (q, J = 7 Hz, 2 H), 6. 6 4 (t, J = 7Hz, 1H), 7.02 (dd, J = 9Hz, 11Hz, 1H), 8.47 (d, J = 7Hz, 1 H), 8.59 (s, 1 H)

 (Example 43)

 7-Black mouth 1-(2, 4-difluoro 5-methyl phenol) 1-6-fluoro 1, 4-dihydro 4- Kiso 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 No. 7 — Black mouth 1 — (2, 4 — Difluorene 5 — Methanol Amino 2) 1 6 — Noro ro 4 1 1,4-hydrogen 1, 8-naphthyridine 1 3 -force 150 ml of a mixture of 1 ml of 3N hydrochloric acid and acetic acid (1: 1, V / V ) And heated under reflux with stirring for 2 hours. 5 ml of distilled water was added thereto, and the mixture was further heated under reflux for 10 minutes, and then allowed to cool, and the precipitate was dispersed in ethanol and collected by filtration, and then ethanol, disopropyle was added. The solid was washed in order, giving 70 mg of the title compound.

Properties: yellow

 BB

 I insect point: 250-25 2 ° C

'HNMR (d ₆ -DMS 0) δ;

 2.69 (d, J = 5Hz, 3Η), 5.90 (brs, 1H), 7.01 (t, J = 8Hz, 1H), 7.

46 (t, J = 11 Hz, 1H), 8.76 (d, J = 8Hz, 1H), 8.99 (s, 1H) [Example 44]

Echinole 11 (2,4-Diphenyle 5-Methylamine) 1 6, 7 — diphnole 1, 4 — dihydro 1 4 1 oxo 1 quinoline 3 — carboxylate:

 Echinore 1 — (3—Amino I, 4,6—Gifnolelo Feninore) 1 6,7—Difnoleo Mouth 1,4, Jihidro 1 4—Oxo 1 The title compound was obtained in the same manner as in Example 42 except that quinoline 13-canolexylate was used.

 Properties: yellow powder

 Melting point: 208-211 ° C

'HNMR (d ₆ -DMS 0) δ;

 1.22 (t, J = 7Η, 3Η), 2.72 (d, J = 4Η, 3Η), 4.2 3 (q, J = 7Η, 2 2) , 5.94-6.004 (m, 1Η), 7.04 (t, J = 8Η, 1Η), 7.19 (dd, J =

4 Η ζ, Ι Ο Η ζ, 1 Η), 7.52 (t, J = 10 Η,, 1 Η), 8.14 (t, J = 10 Η,, 1 Η), 8 .

5 5 (s, 1Η)

 (Example 4 5)

 1-(2, 4-difuzoleo mouth 1 5-methinorea minofe 2 nore) 1 6, 7-diphnoreolo 1, 4-dihydro 1-4 quino Lin 1 3 — Power oleic acid:

 Echinore 11 (2, 4 — Gifnoré Mouth 1 5 — Metnole Aminofen 2) _ 6, 7 — Gifnoreo Mouth 1, 4 — Jihydro 41 The title compound was obtained in the same manner as in Example 43, except for using oxo-quinoline 13-potassium chloride.

Properties: brown powder Melting point:〉 16 4 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

 2.71 (s, 3H), 6.01 (brs, 1H), 7.05 (t, J = 8Hz, 1H), 7.39—7.51 (m , 1 H), 7.5 3 (t, J = 10 Hz,

1 H), 8.34 (t, J = 9 H z, 1 H), 8.90 (s, 1 H)

 (Example 4 6)

 No. 7 — Chlorine 1 — (3 — Dimethylamino 4, 6 — Difluoro phenyl) 1 6-Funole 1, 4 — Dihydro 1 4 1 oxo 1, 8 — naphthyridine 1 3 — carboxylate:

 1-1 (3-Amino 1, 4-6-diphenyle-phenyl) 1-7-Chloro 6-1-octane 4-Oxo 1-1, 4-Jihi Draw 1, 8 — Naphthyridine 1 3 — Forced boxyrate 500 mg with 500 mg of 37% formalin and 1 Oml of 1 , 2—Dichloroethane, 5 ml of methanol, 0.5 ml of acetic acid and hydrogenated with 0.08 g of 10% paradium carbon (64 hours). After the catalyst was filtered off, the filtrate was concentrated under reduced pressure to obtain the title compound.

Properties: yellow powder

Melting point: 15 8-16 3 ° C

 'H NMR (CDC13) δ;

1.41 (t, J = 7Hz, 3H), 2.88 (s, 6H), 4.41 (q, J = 7Hz, 2H), 6. 8 5 (t, J = 7Hz, 1H), 7.04 (dd, J = 9Hz, 12Hz, 1H), 8.47 (d, J = 7Hz, 1 H), 8.5 7 (s, 1 H)

 (Example 4 7)

 7 — Chlorine 1 — (3 — Dimethylamino 4, 6 — Difluoromethyl) 1-6-Fluorine Mouth 1, 4-Dihydro 1 4 1-oxo-1,8-naphthyridine-1 3-potassium oleic acid: ethyl 7 obtained in Example 46 7-clo mouth 1-1-1 (3—dimethinorea 4, 6 — dihydronorfollowing 1-6 — phloreol 4 oxo 1, 4 — dihydro 1, 8 — naphthyridine 3 — ka The entire amount of ruboxylate was added to 4 ml of a mixture of 3N hydrochloric acid and acetic acid (1: 1, VZV), and the mixture was heated under reflux with stirring for 2 hours. The mixture was allowed to cool, concentrated under reduced pressure, and the precipitate was dispersed in ethanol, collected by filtration, washed with ethanol and diisopropynoleatel in that order to give 295 mg of the title compound. Obtained.

Properties: light yellow powder

Melting point: 24.4-2470. C

'HNMR (d ₆ -DMS 0) δ;

 2.79 (s, 6H), 7.41 (t, J = 8Hz, 1H), 7.57 (dd, J = 10Hz, 13Hz, 1H) , 8.7.7 (d, J = 8 Hz, 1 H), 9.04 (s, 1 H)

 (Example 48)

1 — (3 — Amino 1, 4, 6-diphenylene phenyl) — Ί-[(3 S) 1 3 — Aminopyrrolidin 1-1 -yl]-6 — Phenole 1, 4 — Dihydro 4 — Oxo 1, 8 — Naphthyridine 1 3 — Power

 1 — (3 — Amino 4, 6-diphnolelofenyenole) 1 7 — Crole 1 6 — phneolero 4 1 oxo 1, 4 — dihydro 1 1, 8 — Naphthyridine 13-force olevonic acid 130 mg, (3 S) — 3 — Aminopyrrolidine 600 mg, Triethyla Min l OOO mg was added to 650 mg of N, N-dimethylformamide and stirred at 90 for 1 hour. After cooling, 25 ml of ethanol was added, and the mixture was heated under reflux for 5 minutes. After allowing to cool, the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, to obtain 141 mg of the title compound.

Properties: light brown powder

Melting point: 260-266 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.81 (m, 1H), 2.06 (m1H), 5.

36 (brs, 2H), 6.97 (tJ = 8Hz, 1H), 7.35 (t, J = 10Hz1H), 8.06 (d, J = 1 3 H z, 1 H), 8 6 9 (s 1 H)

 (Example 49)

 1-(3-Amino 4, 6-diphnorelofenynore) 1 7 1 [(3 S)-3-aminopyrroline 1 1-dinore]-6- 1,4-Dihydro-1,4-phenyl-1,8-Naphthyridine-3: Carbonic acid triethylamine salt:

1 — (3 — Amino 1, 4, 6 — Gif Noreo Lofeni Nor) 1 7 — Chlorolo 6 — Phenorero 4 — Oxo-1,4-dihydro-1,8-naphthyridine — 3-Carboxylic acid 220 mg, (3S) — 3 — Add 210 mg of aminopyrrolidin 'dihydrochloride and 400 mg of trietinoreamin to l OOO mg of N, N — dimethylformamide, 90. The mixture was stirred with C for 1 hour and 30 minutes. After cooling, 1 Om1 of ethanol was added, and the mixture was heated under reflux for 5 minutes. After allowing to cool, the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order to obtain 220 mg of the title compound.

Properties: light brown powder

Melting point: 245-249 ° C (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 1.06 (t, J = 7 7, 9Η), 1.66 (m, 1Η), 1.92 (m, 1Η), 3.44 (q, J = 7Η) 6, 6Η), 5.35 (s, 2Η), 6.96

(t, J = 8Η ,, 1Η) 7.35 (t, J = 10 0 ζ, 1Η), 8.02 (d, J = 13 8. ζ, 1Η), 8. 6 6 (s, 1Η)

 (Example 50)

 1 1 (3—Amino 4 and 6—Diphenylophenyl) 1 7 1 [(3S) 1 3—Aminopyrroline 1 1–1] — 6 — Phenoleuro-1,4-dihydroxy-4,1-oxo-1,8-Naphthyridine-3—Carbonic acid dihydrochloride:

1 1 (3-amino 4, 6-diphenyl phenyl) 1 7 1 [(3 S)-3-aminopyrrolidin 1-1]-6- Fluoro 1, 4 ヒ 4 4 4 4 1 8 8 — 100 mg of thylidine 13-carboxylate was dissolved in 2.5 ml of 6N hydrochloric acid, and then concentrated under reduced pressure. Ethanol was added to the residue, and the precipitate was crushed and collected by filtration, and washed with ethanol and diisopropyl ether in that order to obtain 97 mg of the title compound. Properties: light brown powder

Melting point: 24 6-250 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 2.09 (m, 1H), 2.22 (m, 1H), 7.

0 3 (brt, 1H), 7.39 (t, J = 10Hz, 1H), 8.12 (d, J = 12Hz, 1H), 8.

30 (brs, 2H), 8.72 (s, 1H) [Example 51]

 1 — (3 — Amino 2, 4 — Diphenylene phenyl) 1 7 1 [(3 S) 1 3 — Aminopyrrolidin 1 1-Inole] — 6 — Phenole mouth 4 — oxo 1, 4 — dihydro 1, 8 — naphthyridine — 3 — carboxyformate:

1 — (3 — Amino 2, 4 — Diphenolic vinyl) 1 7-[(3 S) — 3 — Aminopyrrolidin 1 1 — Tinole] — 6 — Phorenolol 41,4-oxo-1,4-Dihydro1,8-naphthyridine-13 3-potassoleic acid 200 mg, formic acid 200 mg for 1 minute After stirring to the extent, 20 mg of ethanol was added, and the mixture was stirred at 90 ° C for 1 minute. Add 2 ml of ethanol, stir at the same temperature for another 2 minutes, and let stand.The precipitate is collected by filtration, washed with ethanol, and diisopropyl ether in that order. Thus, 154 mg of the title compound was obtained. Properties: light brown powder

 Melting point: 2 23-2 26 ° C

'HNMR (d ₆ -DMS 0) δ;

 1.75 (m, 1H), 2.000 (m, 1H), 5.36 (s, 2H), 6.96 (t, J = 8Hz, 1H),

7.35 (t, J = 11Hz, 1H), 8.04 (d, J = 12Hz, 1H), 8.26 (s, 1H), 9.6 8 (s, 1H)

 (Example 52)

 1 — (3 — Amino 2, 4 — Difluoropheninole) 1 7 1 [(3 S) 1 3 — Aminopyrrolidin 1 1-Inole] — 6 — F Norrero 4 1-oxo 1, 4-dihydro 1, 8-naphthyridine 13 -capronic acid P-toluenesulfonate: 1- (3 — Amino 1, 2, 4 — Difluorophenyl) 1 7 1 [(3S) 1 3 — Aminopyrrolidin 1 1 1] 16 — Fumoleo 1 4 1,4-dihydroxy-1,8-naphthyridine-13-potassolenoic acid 100 mg, p-toluenesulfonate hydrate 5 5 mg was added to 30 mg of N, N-dimethylformamide and stirred for about 5 minutes. To the homogenized solution, 8 ml of diisopropyl ether was added, and the mixture was stirred and allowed to stand, and the supernatant was removed by decantation. Then, lm 1 of ethanol was added, and the mixture was heated under reflux for 2 minutes and allowed to cool. Was.

Properties: light brown powder Melting point: 270 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 2.02 (m, 1H), 2.24 (m, 1H), 2.28 (s, 3H), 3.89 (m, 1H), 5.37 (brs , 2 H), 6.96 (t, J = 7 H z, 1 H),

7.11 (d, J = 8Hz, 2H), 7.35 (dt, J = 2Hz, 12Hz, 1H), 7.47 (d, J = 8H z, 2H), 7.95 (brs, 2H), 8.13 (d, J = 12Hz, 1H), 8.7.2 (s, 1H)

 (Example 53)

 1 — (3 — Amino 1, 4, 6 — Dihydronoreno 1) 1 ー 6 オ 1, 4 — Dihydro 7 — (3 — Hydroxypi Mouth resin-1 1-innole) 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Force

1 — (3 — Amino 4, 6 — Gifnoreo Lofeninore) 1 7 — Chloro 6 — Fuzoleo Mouth 4 — Oxo 1–4, Jihiro — 1, 8 — Naphthyridine 1 3 — Power oleic acid 150 mg, 3 — Hydroxypyrrolidin 100 mg, Triethylamine 10 O mg 550 mg N, N—dimethylformamide plus 70. (: The mixture was stirred for 30 minutes. 8 ml of diisopropyl ether was added, and the mixture was stirred and allowed to stand, and the supernatant was removed with decantation. The ethanol was added and the precipitate was collected by filtration and washed with ethanol and diisopropanolone in that order to obtain 156 mg of the title compound. Properties: colorless powder

 Melting point: 25 1-25 3 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.56 (m, 1Η), 1.70-1.95 (m, 3Η), 2.58-2.96 (m, 4Η), 4.16

(m, 1H), 4.30 (brs, 1H), 5.35 (s, 2H), 6.95 (t, J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H), 8.01 (d, J = 13Hz, 1H), 8.59 (s, 1H) [Example 54]

 1-(3-Amino 1, 4-6-Gifnole Orofeninore) 1 7 1 [(3S, 4S) 1 3-Amino 1-4 1 — レ — — オ 6 6 6 6 6 6 6 1 4 1 1 6 6 6 6 6 1 4 4 4 1 4 — 6

 The title compound was obtained in the same manner as in Example 48 except that (3S, 4S) —3—amino-4-methylpyrrolidinidine dihydrochloride was used.

Properties: light brown powder

_{^{1 HNMR (d 6 - DMSO)}} δ;

 0.93 (d, J = 7 Hz, 3 H), 2.17 (m,

1H), 5.35 (s, 2H), 6.97 (t, J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H), 7.99 (d, J = 12Hz, 1H), 8.65 (s, 1H)

(Example 55) 1 — (3—Amino 1-4, 6—Diphenylophenyl) 1 7-[(3R, 4R) — 3—Amino 4-methylpyrrolidin — 1 ノ レ レ 1 — 6 フ ノ 1, 4 ジ dihydro 1 4 4 oxo 1, 8 ナ naphthyridine 1 3 力 sulfonic acid:

 (3 R, 4 R) — 3 — amino 1-4-methyl pyridine. The title compound was obtained in the same manner as in Example 48 except that dihydrochloride was used.

Properties: light brown powder

Melting point: 2 14-2 17 ° C

'HNMR (d ₆ -DMS 0) δ;

0.93 (d, J = 7Hz ₍ 3H), 2.17 (m, 1H), 5.36 (s, 2H), 6.96 (t, J

= 8Hz, 1H), 736 (t, J = 10Hz, 1H), 7.99 (d, J = 12Hz, 1H), 8.65 (s , 1 H)

 (Example 56)

 1 — (3 — Amino 4, 6 — diphenyl phenyl) 1 7-[(3 S, 4 R) — 3 — Amino 4 — methyl pyrrolidine 1 1] レ — — 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6

 The title compound was obtained in the same manner as in Example 48 except that (3S, 4R) —3—amino-14-methylpyrrolidinine dihydrochloride was used.

Properties: light brown powder

Melting point: 2 3 4 — 240 ° C ¹ HNMR (d ₆ — DMSO) δ;

 0.98 (d, J = 7Hz, 3H), 1.93 (m, 1H), 3.03 (m, 1H), 5.36 (s, 2H), 6.97 (t, J = 8Hz, 1H), 7.37 (t, J = 10Hz, 1H), 8.04 (d, J = 12Hz, 1 H), 8.68 (s, 1 H)

 (Example 5 7)

 1 — (3-Amino 4, 6 — Gifnole orofeninore) 1 7 1 [(3 R, 4 S) — 3 — Amino 4 — Methinole 1-4-dihydro 1, 4-dihydro 1-4-oxo 1, 8-naphthyridine 1 3-force

 The title compound was obtained in the same manner as in Example 48 except that (3R, 4S) —3—amino-1-4—methynolepyrrolidine dihydrochloride was used.

Properties: light brown powder

Melting point: 2 3 7 — 24 1 ° C

_{'HNMR (d 6 - DMSO)} δ;

 0.98 (d, J = 6Hz, 3H), 1.93 (m, 1H), 3.02 (m, 1H), 5.37 (s, 2H), 6.97 (t, J = 8Hz, 1H), 7.37 (t, J = 10Hz, 1H), 8.03 (d, J = 13Hz, 1 H), 8.67 (s, 1 H)

 (Example 58)

1 1 (3—Amino 4 and 6—Gifnole Olofeninor) 1 7 — (3—Amino 1 and 4 and 4 1 Dimethyltin pyrrolidine 1 1 Nore) 1-6-phenol 1-1, 4-dihydro 4-oxo 1, 8-1 naphthyridine 1-3-oleic acid:

 3—Amino-1,4,4—dimethinolepyrrolidin ♦ The title compound was obtained in the same manner as in Example 48 except that dihydrochloride was used. Properties: light brown powder

Melting point: 26 7-26 9 ° C (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 0.86 (s, 3H), 095 (s, 3H), 2.88-3.05 (m, 1H), 5.36 (s, 2H), 6. 9 7 (t, J = 8Hz 1H), 7.38 (t, J = 10Hz, 1H), 8.02 (d, J = 13Hz, 1H), 8.6.6 (s, 1H)

 (Example 59)

 1- (3—Amino4, 6—Gifnolerofenenior) 1 7- [3— (N—EchinoreAminoMetinore) Pyrrolidin 1—I ] — 6 — Fluoro 1, 4-Hydro 4 — Oxo 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 The title compound was obtained in the same manner as in Example 48 except for using 3-((N-ethylaminomethyl) pyrrolidine dihydrochloride). Properties: light brown powder

Melting point: 2 3 5-2 4 4 ° C (decomposition)

1 HNMR (d ₆ -DMS 0) δ;

1.01 (t, J = 7 7, 3Η), 1.61 (m, 1Η), 1.98 (m, 1Η), 2.32 (m, 1Η), 2.54 (q, J = 7 Η,, 2 Η), 5.34 (s, 2H), 6.96 (t, J = 8Hz, 1H), 7.35 (t, J = 110Hz, 1H), 8.02 (d, J = 12 Hz, 1H), 8.67 (s, 1H) [Example 60]

 1 1 (3—Amino 1, 4 and 6—Difnoreo Lofeninore) 1 7-[(3S) -3—Amino pyrrolidine 1 1-yl] — 6—F Norero 1,4-dihydro-1-4 — oxoquinoline 13 — carboxylate:

 3 Add 29 mg of S-(-)-aminopyrrolidine and 68 mg of triethylammine to 1 ml of dimethinoresnorrefoxide, stir for 10 minutes, and add 1-11 (3 — Amino — 4, 6 — difluorophenyl) 1, 6, 7 — difluoro 1, 4, 4 — dihydro 1-oxo-quinoline Add 80 mg of 3-strength oleonic acid and add 100. Stirred with C for 2 hours. After allowing to cool, getyl ether was added to the reaction solution, and the supernatant was removed. Ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 76 mg of the title compound were obtained.

Properties: colorless powder

Melting point: 2 1 3-2 2 1 (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.6 2-1.76 (m, 1H), 1.8 8 — 2.

0 6 (m, 1 word), 3.08 (b rs, 1 word), 5.

5 3 (s, 2 Η), 5.92 (d, J = 8 Η ζ, 1 Η),

7.03 (t, J = 8Η, 1Η), 7.50 (t, J = 11 1, 1Η), 7.85 (d, J = 14 4, 1 H), 8.6 1 (s, 1 H)

 (Example 6 1)

 1 — (3 — Amino 4, 6 — diphenyl phenyl) 1 7-[(3 S, 4 S) 1 3 — Amino 4 — methyl pyrrolidine 1 — ィ レ — — — 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 1 1 1 1 1 1

 The title compound was obtained in the same manner as in Example 60, except that (3S, 4S) —3—amino-4—methynolepyrrolidine was used. Properties: brown powder

Melting point: 1 96-202 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 0.95 (d, J = 7 Hz, 3 H), 222 (brs, 1 H), 5.53 (s, 2H), 58 8 (d, J

= 5 Hz, 1 H), 7, 0 2 (m, 1 H), 7.50 (t, J = 9 Hz, 1 H) 7.85 (d, J = 14 Hz, 1 H), 8.60 (s 1 H)

 (Example 6 2)

 1 — (3 — Amino 4, 6 — Di-Finorelo-Fennino) 6 — Phenoleo 1, 4 — Di-Hydro 1-4-oxo 1 7 — (D 1 1-inole) 1 quinoline 1 3—force

 The title compound was obtained in the same manner as in Example 60 except that pyrrolidine was used.

Properties: colorless powder

Melting point: 2 64-2 68 ° C (decomposition)

'HNMR (d for DMSO) δ; 1.89 (brs, 4H), 5.52 (s, 2H), 5.97 (d, J = 8Hz, 1H), 7.03 (t, J = 8H z, 1H), 7.49 (t, J = 10Hz, 1H), 7.85 (d, J = 14Hz, 1H), 8.62 (s, 1 H)

 (Example 6 3)

 1 — (3 — Amino 4, 6 — difluorophenyl) — [[(1 S, 6 S) — 2, 8 — diazabicyclo [4.3. 0] NON 1-8 — INNO 1) 6 — FUNOROH 1, 4-HYDRO — 4 — OXO

 The title compound was obtained in the same manner as in Example 60 except that (1S, 6S) 12,8-diazabicyclo [4.3.0] nonane was used.

Properties: colorless powder

Melting point: 2 26-23 3 ° C (decomposition)

'HNMR (d ₆ — DMSO) δ;

 1.5 3-1.8 1 (m, 4 H), 2.6 3 (brs,

1Η), 2.88 (brs, 1Η), 3.5 1 (m,

2), 3.83 (brs, 2), 5.57 (s,

2), 5.97 (d, J = 8 ζ 1 H), 7.

0 5 (t, J = 9 Η ζ, 1 Η), 7 5 1 (t, J

= 1 0 Η 1, 1 Η), 7.92 (d, J = 14 Η ζ,

1), 8.6.5 (s, 1)

 (Example 6 4)

1 1 (3—Amino 4 and 6—Difluorophenyl) 1 7 1 [(3 S) — 3 — Aminopyrrolidin 1 1 ノ レ] — 6 8 6, 8 フ Diphenyle 1, 4 4 Dihydro 1 4 oxoquino Lin 3 — carboxylic acid:

 1-(3-Amino 1, 4, 6-diphnoreolofenynore) 1, 6, 7, 8 — Trifnolero 1, 4-dihydro 4-Oxo 1 The title compound was obtained in the same manner as in Example 60, except that quinoline-3-3-capillonic acid was used.

Properties: brown powder

Melting point: 204-210 ° C (decomposition)

 'H N M R (de-D M S O) δ;

 1.67 (m, 1H), 1.95 (m, 1Η), 5.42 (s, 2Η), 7.08 (m, 1Η), 7.37 (t , J = 10 Η,, 1 Η), 7.78 (d, J = 14 Η, 1 Η), 8.45 (s, 1 Η)

 (Example 65)

 1 — (3 — Amino 4, 6 — Diffusion / Olofeni / North) 1 7 1 (3 — Hydroxypyrrolidin 1-1 / North) 1 6, 8 — Diphenyle 1, 4-dihydro 4 oxo monoquinoline 3 — oleic acid:

 The title compound was obtained in the same manner as in Example 60, using 3 -hydroxypyrrolidin.

Properties: light yellow powder

Melting point: 1 4 4 1 1 5 2 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

1.81 (m, 2H), 3.79 (m, 1H), 4. 29 (brs, 1H), 5.000 (s, 1H), 5.44 (s, 2H), 7.09 (t, J = 8Hz, 1H), 7. 39 (t, J = 10Hz, 1H), 7.80 (d, J = 14Hz, 1H), 8.47 (s, 1H) [Example 66]

 1 — [3 — Amino 2, 4 — Difluorophenyl] — 7 — [(3 S) — 3 — Aminopyrrolidin 1 — yl] — 6 — Phenoleuro-1,4-dihydro-1-41,8-naphthyridine-13-force oleic acid:

 1 1 [3 — Amino 2, 4 — Gifnoreo Lofeninore] — 7 — Krollo 6-Fluoro 1, 4 — Jihydro 1 4 — Oxo — The title compound was obtained in the same manner as in Example 48 except that 1,8-naphthyridine-13-force oleic acid was used.

Properties: light brown powder

Melting point: 26 8-27 2 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

 1.79 (m, 1 H), 2.05 (m, 1Η), 5.58 (s, 2Η), 6.84 (m, 1Η), 7.11 (t , J = 10 Η,, 1)), 8.07 (d, J = 13 Hz, 1 Η), 8.69 (s, 1 Η)

 (Example 6 7)

1 1 [3 — Amino 2, 4 — Diphenylene Lofeninole] 1 7 1 [(3 S, 4 S) 1 3 — Amino 4-methyl pyrrolidin 1 1 レ レ — — 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 1 — [3-amino 2, 4 — diphenyl phenyl] — 7 — chloro 6 — phenol 1, 4 — dihydro 4 oxo — The title compound was obtained in the same manner as in Example 48 except that 1,8-naphthyridine-13-force oleic acid was used.

Properties: light brown powder

'HNMR (d ₆ — DMSO) δ;

 0.91 (brd, 1H), 2.14 (m, 1Η), 5.58 (s, 2Η), 6.83 (m, 1Η), 7.10 (t , J = 10 Η,, 1 Η), 8.02 (d, J = 12 Hz, 1 Η), 8.65 (s, 1 Η)

(Example 68)

 1 — (3 — Amino 4, 5 and 6 — Trifnorolephane) 1 7 — [(3 S) — 3 — Aminopyrrolidine 1 — Inole] ― 6 — phenol 1 1, 4-hydr 1 4 1 oxo 1, 8 — naphthyridine 1 3 — oleic acid:

 1 1 (3—Amino 1, 4, 5 and 6—Trif Noreo Lo Feninore) — 7—Kuro mouth 1 6—Fnoreo 1 and 4—Dihydro 4—Oki The title compound was obtained in the same manner as in Example 60 except that sodium 1,8-naphthyridine-13-potassium oleic acid was used.

Properties: brown powder

Melting point:〉 25 6 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

1.58-1.84 (m, 1H), 1.84-2.23 (m, 1H), 5.74 (s, 2H), 6.81 (t, J = 5 Hz, 1 H), 8.03 (d, J = 12 Hz, 1 H), 8.73 (s, 1 H)

 (Example 6 9)

 1 1 (3-Amino 4, 5, 6-Trif Norole Lofeninole) 1 7-[(3S) 1 3-Amino pyrrolidine 11 1] 1 6 — Phenoleuro 1, 4 — Dihydro 1 4 — Oxo monoquinoline 13 Mono oleic acid:

 1 1 (3—Amino 1,4,5,6—Trifluorophenyl) -6,7—Difluoro1, 4 -Dihydro1 4 —Oxo Iki The title compound was obtained in the same manner as in Example 60 except that norrin-3-carboxylic acid was used.

Properties: brown powder

Melting point:> 270 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.61-1.81 (m, 1H) 1.89-2.15 (m, 1H), 5.88 (s, 2 layers), 6.88

(brs, 1Η), 7.85 (d, J = 15 5, 1 1), 8.69 (s, 1Η)

 (Example 70)

 1 — (3 — Amino 1, 2, 4, 6 — Trifnorolelophenyl) — 7 — [(3 S) 1 3 — Aminopyrrolidin 1 1 — Tinole] 1 6 — phenol 1, 4 — dihydro 1 4-1 oxo 1, 8 — naphthyridine 1 — force oleic acid:

1 — (3—Amino 2, 4, 6-trifolenorrophenyl) — 7 — Black mouth 6 — Fnoreo mouth 1, 4-Dihydro 4 — Kiso 1, 8 — Naphthyridine 1 3 — Force oleic acid 7 O m ff Dissolve in 1 ml of dimethyl phenol, and add 3 (S) —3—aminopyrrolidin 0.018 ml triethylenoamine 0.04 ml, Stirred at 80 ° C for 1 hour. The diethyl ether was added to the reaction solution, and the decantation was repeated twice. A small amount of ethanol was added to the residue, and the mixture was refluxed for 10 minutes, and the precipitated solid was collected by filtration and washed with diethyl ether to obtain 51 mg of the title compound.

Properties: light brown powder

 i insect point: 2 7 3 — 2 7 7 ° C

 'H N M R (de-D M S O) δ;

 1.75-1.78 (m, 1H), 200-2.18 (m, 1Η), 5.46 (brs, 1H), 7.39 (t, J = 10 Η ζ, 1 Η), 8 08 (d, J = 13 Η ,, 1 Η), 8.97 (s1H) [Example 71]

 1 — (3 — Amino 1 6 — Chlorine 4 — Phenylophenyl) — 7 — [(3 S) — 3 — Aminopyrrolidin 1 1 6 — Fluorine mouth 1, 4 — dihydro 4 1 oxo 1, 8 — naphthyridine 1 3 — force oleic acid:

 1 — (3 — Amino 6 — Black mouth 4 — Fnoreo Lofeninore) — 7 — Black mouth 6 — Fnoreo mouth 1, 4 — Dihydro 1-4 The title compound was obtained in the same manner as in Example 70 except that sodium 1,8-naphthyridin-13-carboxylate was used.

Properties: light tan powder

Melting point: 2 4 9 — 25 2 ° C ¹ HNMR (d ₆ -DMS 0) δ;

 1.74-1.95 (m, 1H), 2.00-2.16 (m, 1H), 5.69 (brs, 2H), 7.00 (d, J = 9 Hz, 1 H), 7.47 (d, J = ll Hz, 1 H), 8.02 (d, J = 12 Hz, 1 H), 8.61 ( s, 1 H)

 (Example 7 2)

 1 — (3 — Amino 6 — Black mouth 4 — Phenolelophenyl) 1 7 — [(3 S) — 3 — Aminopyrrolidin 1 1 — Tinole 1 6 — phenol 1, 4-hydro 1 4 — oxo 1 quinoline 3 — carboxylate:

 1 — (3 — Amino 6 — Chlorine 4 — Phorenolophenyl) — 7 — Kroguchi 1 6 — Phonore 1, 4 — Jihdro 1 4 1 year old The title compound was obtained in the same manner as in Example 70, except that oxoquinoline-3- 3-capronic acid was used.

Properties: light red powder

Melting point: 17 7-18 2 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

 1.59-1.75 (m, 1H), 1.86-2.07 (m, 1H), 5.78 (d, J = 7Hz, 1H), 5 .89 (brs, 2H), 7.06 (d, J = 9Hz, 1H), 7.60 (d, J = 11Hz, 1H), 7.86 ( d, J = 14 Hz, 1 H), 8.56 (s, 1 H)

(Example 73) 1 — (3 — Amino 1 4 — Chlorine 6 — Phenorelofeninole)-7-[(3 S) 1 3 — Aminopyrrolidin 1 1] 6-Phenylo mouth 1, 4 — dihydro 1 _ 4 oxo 1, 8 — naphthyridine 1 3 — carboxylic acid:

 1 — (3 — Amino 1 4 — Black Mouth 1 6 — Holo Leno Feninole) 1 7 — Black Mouth 1 6 — Homo Leo Mouth 1, 4 — Dihydro 1-4 The title compound was obtained in the same manner as in Example 70, except that sodium 1,8-naphthyridine-13-potassic acid was used.

Properties: brown powder

Melting point:> 258 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 1.53-1.80 (m, 1H), 1.83-2.06 (m, 1Η), 5.56 (brs, 2Η), 6.99 (d, J = 7 Η ζ, 1 Η), 7.48 (d, J = 10 Η,, 1 Η), 8.02 (d, J = 13,,,

1)), 8.68 (s, 1 Η)

 (Example 74)

 1 1 (3-Amino 1-4-Fluoro 2-methyl phenyl)-7-[(3S) 1 3-Amino pyrrolidine 1-1-Ino] 1 6 — Phenole 1, 4-Hydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Potassium

1 — (3 — Amino 4 — Fluorine 2 — Methinolephenyl) 1 7 — Chloro 6 — Phenole 1, 4 — Dihydro 1 4 — Oxo The title compound was obtained in the same manner as in Example 70 except that oleic acid was used instead of -1,8-naphthyridine-13-force. Properties: light brown powder

 Melting point:〉 16 5 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 1.53-1.73 (m, 1H), 1.74 — 1.98 (m, 1Η), 1.83 (s, 3Η), 5.25 (br, 2Η), 6.75 (d, J = 9Η, 1Η), 7.09 (d, J = 13 1, 1Η), 8.02 (d, J = 1 33) Η 1, 1)), 8.48 (s, 1 Η) [Example 75]

 7-[(3 S) — 3 — Aminopyrrolidin 1 1 — yl] 1 1 — (2,4-Diphenylole 5 — Honoré Minorea Minofe 2) One 6 — phenolic mouth 1, 4-dihydro 4-oxo 1, 8-naphthyridine 1 3-force oleic acid:

 7 — Crawl 1 — (2, 4 — Diffusion 5 — Diffusion 2 1) 6 — Drift 1, 4, 4 4-oxo-11,8-naphthyridine-13-force The title compound was obtained in the same manner as in Example 48 except that oleic acid was used.

Properties: light brown powder

Melting point: 2 18-22 5 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.62 (m, 1H), 190 (m, 1Η), 7.72 (t, J = 10 0, 1Η), 8.01 (d, J = 13 Η ,, 1 1), 8 3 4 (s, 1Η), 8.

3 8 (t, J = 8 Η,, Η), 8.71 (s, 1 Η)

(Example 76) 7 — [(3 S, 4 S) 1 3 — Amino 4 — Methyl pyrroline 1 1 ノ】 1 1 — (2, 4 — Difnoreo 1-5 — Hole 1 6 — Fusoleol 1, 4 — Dihydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Power oleic acid : 7 — Chlorine 1 — (2, 4 — Diphnoreoroll 5 — Honoremilamiminofe 2) 1 6 — Phonore mouth 1, 4 — Dihydro 1 4 —Oxo-1,8—Naphthyridine-13—force The title compound was obtained in the same manner as in Example 54 except that oleic acid was used.

Properties: colorless powder

Melting point: 2 15-2 16 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 0.92 (brd, 3H), 2.15 (m, 1Η), 7.71 (t, J = 10 0Η, 1Η), 8.01 (d, J = 1 2 Η ζ, 1 Η), 8.34 (s, 1 Η), 8.38 (t, J = 8 Η ζ, 1 Η), 8.78 (s, 1 Η)

(Example 7 7)

 7 — [(3 S) — 3 — Aminopyrrolidin 1 1 1) — 1 — (3 — Benzoinoramino 1, 4, 6 — Difzoleo ) 1-6-Fluorine 1-4, 4-Hydro 4-Oxo 1, 8-Naphthyridine 1-3-Forced oleic acid:

1-(3-Benzoinoreminoru 4, 6-Diphnorelo-Fennore) 1 7-Chloro 6-Phenolero 1, 4-Dihydro 1 4 The title compound was obtained in the same manner as in Example 48 except that oxo-1,8-naphthyridine-13-potassium oleic acid was used. Properties: light brown powder Melting point: 1997-200 ° C

¹ HNMR (de-DMSO) δ;

 1.65 (m, 3H), 1.92 (m, 1H), 7.51-7.63 (m, 3H), 7.72 (t, J = 10H z, 1 H), 7.94-8.07 (m, 4 H),

8. 7 8 (s, 1 H)

 (Example 7 8)

 7 — [(3 S) 1 3 — Aminopyrrolidin 1 1-in-no-re] 1 1 — (2, 4 — Diph-noreo 1- 5 — Methinole-a-minofenil) — 6 — Phenoleuro-1,4-dihydro-1-4 — Oxo-1,8-naphthyridine-1 3 — Force oleic acid:

 7 — Chromo 1 — (2, 4 — Difluoro 1 5 — Methinole Aminofn 2) 1 6 — Fluoro 1, 4 — Dihydro 1 4 — The title compound was obtained in the same manner as in Example 48 except that oxo-1,8-naphthyridine-13-forcezoleic acid was used.

Properties: light brown powder

Melting point: 25 6-25 8 ° C (decomposition)

1 HNMR (d ₆ — DMSO) <5;

 1-63 (m, 1H), 1.91 (m, 1H), 2.70 (d, J = 5Hz, 3H), 5.79 (brs,

1H), 6.96 (t, J = 8Hz, 1H), 7.39 (t, J = 10Hz, 1H), 8.02 (d, J = 12 Hz, 1H), 8.68 (s, 1H) [Example 79]

7 — [(3 S) 1 3 — Aminopyrrolidin 1 1 1 — (2, 4 — diphenyl phenol 5 — methyl phenol) — 6 — phthalone Lin 3 — Power acid:

 1 — (2, 4 — diphenyl phenol 5 — methinorea minophenyl) 1, 6 — diphenyl phenol 1, 4 — dihydro 1 4 — oxo The title compound was obtained in the same manner as in Example 60 except that carboxylic acid was used.

Properties: brown powder

Melting point: 2 19-2 26 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.59-1.78 (m, 1H), 1.9 1-2.07 (m, 1Η), 2.70 (d, J = 5Η, 3Η), 5 9 1-6.0 .04 (m, 1 1), 7.04 (t, J = 8Η, 1Η), 7.54 (t, J = 11 1, lH), 7.86 (d, J = 14Hz, lH), 8.

6 3 (s, 1 Η)

 (Example 80)

 7 — [(3 S) — 3 — Aminopyrrolidin 1 1-yl]-1 — (3 — Dimethylnorrea Minor 4, 6 — Diphnoreolofeninole) — 6 — Fluorine 1-, 4-dihydro 1-, 4-oxo 1, 8 — Naphthyridine 1 3 — Force oleic acid:

7 — Black mouth 1 1 1 (3 — Dimethylamino 4, 6 — Difluoro mouth 1 二 2) 1 6 — Black hole 1, 4 — Dihydro 4-oxo-1,8-naphthyridin-13-force The title compound was obtained in the same manner as in Example 48 except that oleic acid was used. Properties: light brown powder

 Melting point: 2 4 8-25 1 (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 1.63 (m, 1H), 1.91 (m, 1Η), 2.77 (s, 6Η), 7.36 (t, J = 8Η, 1Η),

7.49 (t, J = 10Η, 1Η), 8.02 (d, J = 13Η, 1Η), 8.74 (s, 1Η) [Example 8 1]

 7-[(3 S) 13-Aminopyrrolidin 11-1]-1-[2, 4-Difluoro 1-5-(L-Glycinoremino) 1-6-Fluoro-1,4-dihydro-1-4-oxo-1,8-Naphthyridine 1-3-Forced boronic acid:

 1 1 (3—Amino 4 and 6—Gifnoreo Lofeninor) 1 7 1 Chloro 6—Horenoro 4 1 Oxo 1 1 and 4—Jihydro 1,8-naphthyridine-13-caprolubonic acid 700 mg, (3S) -3- (t-butoxycanolevonylamino) pyrrolidine 450 mg, triethyl Add 400 mg of Noreamine to 2 ml of N, N-dimethylformamide and add 70 mg. The mixture was stirred at C for 30 minutes. 30 ml of diisopropyl ether was added, the mixture was stirred and allowed to stand, and the supernatant was removed with decantation. This was used for the next reaction as it was.

N — B oc — Glycine 350 mg, N — Methylene phenol olein 21 O mg was added to 1 O ml of dichloromethane and brought to 120 ° C. Under agitation, 270 ml of isoformin formate was added and stirred for 20 minutes. Cool the solution to —60 1 — (3 — Amino 4, 6 — Gifnoreolofeninole) 1 7-[(3 S) — 3 — (t-butoxycanoleponyla mino) pyrrolidine ] — 6 — Phenoleuro 4 — Oxo 1, 4-dihydro 1,8 -naphthyridin-3-carboxylic acid in 10 ml of dichloromethane Dissolved and added. The temperature was slowly returned to room temperature, and the mixture was heated under reflux for 2 hours. The mixture was allowed to stand at room temperature overnight, 50 ml of black-mouthed form and 10 ml of distilled water were added, the layers were separated, dried over magnesium sulfate anhydride, and concentrated under reduced pressure. One-third of the foamed residue was dissolved in 6 ml of acetonitrile, and 1.5 ml of a 4N hydrogen chloride dioxane solution was added, followed by stirring at room temperature. . A precipitate was formed in about 1 minute. The mixture was stirred overnight, and the precipitate was collected by filtration.The precipitate was dissolved in about 4 ml of distilled water, and a 10% aqueous solution of sodium hydroxide was added little by little to pH 8. To form a precipitate. The mixture was heated under reflux for 1 hour, allowed to cool, and the precipitate was collected by filtration and washed with distilled water, ethanol and diisopropyl ether in that order to obtain 19.3 mg of the title compound as a colorless powder.

Properties: colorless powder

Melting point:〉 270 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.65 (m, 1H), 192 (m, 1H), 7.73 (t, J = 11Hz, 1H), 8.04 (d, J = 13 Hz, 1H), 838 (m, 1H), 8.78 (s, 1H)

(Example 82) 1 1 (3—Amino 4 and 6—Gifnoreo Lofenino) 1 6 1 Fluoro 7 — [(3S) 1 3— (L—Noryllamino) [Roledin 1 1 -inole]]-1,4 -Hydrogen 4 -oxo-1, 8 -naphthyridine 1 3 -force

N — B oc — L — Valine 220 mg, N — Methylene morpholin 106 mg in 5 ml of dichloromethane, bring to 120 ° C. With stirring, the mixture was added with isoforminol chloroformate 1401 and stirred for 20 minutes. The solution is cooled to —60 ° C, and ethyl 7 — [(3S) —3—aminopyrrolidin 1—inno] —1— (2, 4— Phenole mouth 1 5 — Honoreminoreaminofujin) 1 6 — Phonoole mouth 1-4-oxo 1, 4-dihydro 1, 8-naphthyridine 1 3 — Added 475 mg of carboxylate dispersed in 1 O ml of dichloromethane. The temperature was slowly returned to room temperature, and then the mixture was stirred at 40 ° C for 30 minutes. 20 ml of clog mouth form and 10 ml of distilled water were added, liquid separation was performed, and the mixture was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. One half of the residue solidified into a foam was added to a mixed solution of 3 ml of 1N hydrochloric acid and 3 ml of ethanol, and the mixture was stirred at 100 ° C for 1.5 hours. The mixture was concentrated under reduced pressure, 3 ml of 1 N hydrochloric acid was added to the residue, and the mixture was stirred at 100 ° C for 40 minutes. The mixture was concentrated under reduced pressure, and the residue was dissolved in 2 ml of distilled water. A 10% aqueous solution of sodium hydroxide was added little by little to neutralize the solution to a pH of about 8 to generate a precipitate. Add 2 ml of ethanol, heat to reflux for 30 minutes, allow to cool, collect the precipitate by filtration, wash with ethanol and diisopropyl ether in that order, and obtain 141 mg of the title compound. I got Properties: colorless powder

Melting point: 16 2-16 7 ° C

_{^{1 HNMR (d e - DMSO)}} δ;

 0.78 (d, J = 7Hz, 3H), 0.70 (dJ = 7Hz, 3H), 1.71-1.92 (m, 2H)

1.95-2.10 (m1H), 2.88 (dJ = 6Hz, 1H), 4.32 (brs, 1H) 5.35 (s2H) , 6.95 (t, J = 8 Hz 1 H), 7.35 (t, J = 10 Hz, 1 H), 8.06 (d, J = 12 Hz, 1 H), 8.69 (s,

1H)

 (Example 83)

 1 1 (3—Amino 1 4 6—Gifnoreo Lofenino) 1 6—Phoneole 7 — [(3S) —3— (L—Linorea Mino) 1-4-dihydro 1-4-oxo-1, 8-naphthyridine 1 3-force monomonone sulfone Acid salt:

1 1 (3 — amino 4 6 diphenyl phenyl) 1 6 — phenol 7 — [(3S) 1 3 — (L linole amino) 1 1 4 4-dihydro 4 1 -oxo 1-8-naphthyridin-1-3-carboxylic acid 2 15 mg, 24 mg of the medium To the mixture was added 4 ml of ethanol together with the acid, and the mixture was stirred under reflux with heating for 30 minutes. The mixture was allowed to cool, the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, and air-dried to obtain 211 mg of the title compound. Properties: colorless powder

 Melting point:> 270 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 0.87 (d, J = 7Η, 6Η), 1.84 — 2.18 (m, 3Η), 2.31 (s, 3Η), 3.45

(brs, 1Η), 4.36 (brs, 1Η), 5.36 (s, 2Η), 6.96 (t, J = 8Η, 1Η), 7.32 (m, 1Η), 8.06 (brs, 2Η), 8.09 (d, J = 12 2, 1 1), 8.64 (d, J = 7Hz, 1 Η), 8. 7 1 (s, 1 Η)

(Example 84)

 1 — (3 — Amino 4, 6 — Gifnole Orofeninor) 1 — 6 — Fnoreo Mouth 1 — 7 — [(3 S)-3-(L — Mouth ) Pyrrolidine 1 1 — dihydro] — 1, 4-dihydro 1 4 — oxo — 1, 8 — naphthyridine 1 3 — phenolic acid:

 The title compound was obtained in the same manner as in Example 82, except for using N-B0c-L-leucine.

Properties: light brown powder

Melting point: 1 4 9 1 15 4 ° C

_{1 HNMR (d 6 - DMSO)} δ;

0.7 (d, J = 7Hz, 3H), 0.82 (d, J = 7Hz, 3H), 1.14-1.37 (m, 2H), 1 .5 4-1.65 (m, 1H), 1.79-1.94 (m, 1H), 1.95-2.10 (m, 2H), 3.1 0 (t, J = 7 Hz, 1 H), 4.28 (brd, 1H), 5.35 (s, 2H), 6.96 (t, J = 8Hz, 1H), 7.34 (t, J = 10Hz, 1H), 8.05 (d, J = 12Hz, 1H), 8.69 (s, 1H)

 (Example 85)

 1-(3-Amino 1-4, 6-Gifnoreo Lofenino) 1 7-(3-Metinore Aminopipe Ridino) 1-6-Finole Mouth 1, 4- Dihydro 4 _ oxo 1, 8-naphthyridine 1 3-force oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that 3-methylaminopiperidine 'dihydrochloride was used.

Properties: light brown powder

Melting point: 240-242 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.23-1.46 (m, 2H), 1.62-1.87 (m, 2H), 2.11 (d, J = 9Η, 3Η), 3 8 2-4. 18 (m, 2 layers), 5.36 (s,

2 Η), 6.98 (t, J = 7 Η, 1 Η), 7.

3 9 (m, 1 Η), 8.09 (d, J = 14 Η, 1 Η), 8.7 1 (s, 1 Η)

 (Example 86)

1 1 (3—Amino 4 and 6—Gifnole orophenyl) — 7— (3—Medium or aminopyridine) 1—6—F Luo 1, 4 -Hydroxy 1 4-1 oxo quinoline 1 3 —Carbonic acid: The title compound was obtained in the same manner as in Example 60 except that 3-methylamino piperidin 'dihydrochloride was used.

 Properties: colorless powder

 Melting point: 25 4 — 25 8 ° C (decomposition)

1 HNMR (d ₆ -DMS 0) δ;

 1.62 (m. 2H), 1.85 (m, 1Η), 1.99 (m, 1Η), 2.55 (s, 3Η), 2.91 (m , 1Η), 5.58 (s, 2Η), 6.52 (d, J = 7ΗΗ, 1Η), 7.08 (t, J = 8Η 8, 1Η), 7.5 2 (t, J = 10 1, 1 1), 8.02 (d, J = 13Η, 1Η), 8.76 (s, 1Η)

 (Example 8 7)

 1 — (3 — Amino 1, 4, 6-diphnoreolofenyno) 1 7-piperadino 1 6 — phneorolo 1, 4-dihydro 1 4-oxo 1, 8 — Naphthyridine 1 3 — Force oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that piperazine was used.

Properties: light brown powder

Melting point: 1 74-18 4 (decomposition)

1 HNMR (d ₆ — DMSO) δ;

2.69 (m, 4H), 3.56 (m, 4H), 5.37 (s, 2H), 6.98 (t, J = 7Hz, 1H), 7.37 (t, J = 10Hz, 1H), 8.11 (d, J = 13Hz, 1H), 8.73 (s, 1H) (Example 8 8)

 1 — (3 — Amino 1, 4, 6 — Gif Norole Lofenyen) 1 7 — (3, 5 — Dimethyl Norpe Bipe La Gino) 1 6 — Funolero 1, 4 --Hydro-4 1-oxo-1, 8-Naphthyridine-1 3--force

 The title compound was obtained in the same manner as in Example 48 except that piperazine was used.

Properties: light brown powder

Melting point: 25 1-25 6 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 0.96 (brs, 6 H), 2, 57-2.90 (m, 4), 4.08 (m, 2 Η) 5.39 (brs, 2 Η), 6. 9 8 (t, J = 8Η, 1Η), 7.41 (t, J = 11 1, 1 1), 8.16 (d, J = 13Hz, 1H) , 8.78 (s, 1st)

(Example 8 9)

 1 — (3 — Amino I, 4, 6 — diphnolelophenyl) 1 7 — pipera dino 1 6 — funeole 1, 4 ー dihydro 1 4-oxo 1-quinoline 1 3 — carboxylic acid:

 The title compound was obtained in the same manner as in Example 60 except for using pyrazine.

Properties: light yellow powder

Melting point: 19 2-200 ° C

_{'HNMR (d 6 - DMSO)} <5;

3.14 (m, 4H), 3.25 (m, 4H), 5. 5 8 (brs, 2H), 6.48 (d, J = 7Hz, 1H), 7.08 (t, J = 8Hz, 1H), 7.51 (t, J = 10 Hz, 1 H), 8.02 (d, J = 13 Hz, 1 H), 8.75 (s, 1 H) [Example 90]

 1 — (3 — Amino 1, 4, 6 — Jifnoreo Lofenyinore)-Ί 1 (3 — Metinore Bipe La Gino) 1 — 6 — Funoreo 1, 4 — Jihi Dro 4-oxo monoquinoline 13-Power oleic acid dihydrochloride 3-methyl biperazine 35 mg, triethylamine 120 mg was added to dimethyl alcohol Add 1 ml to the mixture, stir for 10 minutes, and add 1 (3-amino 4, 6-diphenyl phenyl) 1, 6-7-difluoro 1, 4- Dihydro 4 — oxoquinoline — 3 — Potassium acid 80 mg, 100 The mixture was heated and stirred at C for 2 hours. After cooling, getyl ether was added to the reaction solution, and the supernatant was removed. Ethanol and hydrochloric acid were added to the residue, and the mixture was stirred at room temperature for 30 minutes. The solution was concentrated under reduced pressure, and ethyl ether was added to the residue. The solid was collected by filtration and washed with dimethyl ether. 30 mg of the title compound were obtained.

Properties: light yellow powder

Melting point: 206-211 ° C (decomposition)

1 HNMR (d ₆ -DMS 0) δ;

1.26 (d, J = 7Η, 3Η), 2.85-3.02 (m, 1Η), 6.5 1 (d, J = 7Η, 1Η), 7.08 (t, J = 8 Hz, 1 1), 7.5 2 (t, J = 10 Hz, 1 H), 8.04 (d, J = 13 Hz, 1 H), 8.76 (s, 1 H)

 (Example 9 1)

 1 1 (3-Amino 4, 6-Diphnoreolophenyl) 1 7 1 (3, 5-Dimethylnorepipe la Gino) 1 6-Funoleo mouth 1, 4 — Dihydro 1 4 1 year old Kiso 1 quinoline 1 3 — Forced boronic acid:

The title compound was obtained in the same manner as in Example 60 except for using 3,5-dimethinolebiperazine.

Properties: colorless powder

Melting point: 202-210 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

 1.17 (brs, 6H) 27 4 (m, 1H), 3.54 (m, 2H), 55 7 (s, 2H), 6.

5 0 (d, J = 7 Η ζ 1 Η), 7.08 (t, J = 8 Η ζ, 1 Η), 752 (t, J = 10 Η,, 1 Η), 8. 0 2 (d, J = 13 Η 1, 1 Η), 8.75 (s, 1 Η)

 (Example 9 2)

 1 — (3 — Amino 6 — Chlorine 4 — Phenolelo Feninore) 1 6 — Phenoole 7 — Pipette Radino 1, 4 — Dihydro 1 4 — Oxiso 1, 8 — Naphthyridine 1 3 — Potassic acid:

1 1 (3—Amino 6—Chloro 4—Horeno Lo Feninole) — 7—Chloro 6—Horono 1—4, —Dihydro 1—4—Oki Sodium 1, 8 — Naphthyridin 13 — Force Dissolve 10 mg of oleic acid in 8 ml of dimethyl sulfoxide, and add 12 mg of piperazine. Was added and stirred at 80 ° C for 1 hour 30 minutes. The ethyl ether was added to the reaction solution, and the decantation was repeated twice. A small amount of ethanol was added to the residue, and the mixture was refluxed for 10 minutes, and the precipitated solid was collected by filtration and washed with ethyl ether to obtain 19 mg of the title compound.

 Properties: brown powder

 Melting point: 190 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 2.88 (s, 4 4), 3.65 (s, 4H), 5.72 (s, 2H), 7.01 (d, J = 5Hz, 1H),

7.46 (d, J = 11Hz, 1H), 8.17 (d, J = 13Hz, 1H), 8.71 (s, 1H) [Example 9 3]

 1-(3-Amino 1-6-Chloro 4-Fnoreolo Feninore) 1-6-Fhonolero 7-Piperazino 1, 4-Hidro 1 4 1 Kisoquinoline 3 — Force oleic acid:

 1 1 (3-Amino 1-6-Black 1-4-Funolero Lo Feninole) 1 7-Black-1-6-Funo 1, 4-1-1-4 The title compound was obtained in the same manner as in Example 92, except that oxoquinolin-3- 3-carboxylic acid was used.

Properties: light yellow powder

Melting point: 2 28-23 7 ° C

'HNMR (d ₆ -DMS 0) δ;

2.81 (s, 4H), 5.91 (brs, 2H), 6.30 (d, J = 7Hz, 1H), 7.10 (d, J = 10 Hz, 1 H), 7.6 1 (d, J = 11 Hz, 1 H), 7.97 (d, J = 12 Hz, 1 H), 8.6 9 (s, 1 H)

 [Example 94]

 1-(3-Amino 1-4 1 mouth 1-6-Phenorelo-Feninole)-6-Funoleo-1-7-Piperazino 1,4-1-1-4 Kiso 1, 8 — Naphthyridine 1 3 — Power

 1 — (3 — Amino 1 4 — Black Mouth 1 6 — Holo Leno Feninole) — 7 — Krollo 6 — Holo Leno 1, 4 — Dihydro 4 The title compound was obtained in the same manner as in Example 92 except that sodium 1,8-naphthyridin-13-carboxylate was used.

Properties: yellow-brown powder

 i insect point: 270. C

'HNMR (d ₆ -DMS 0) δ;

 2.87 (brs, 4H), 5.59 (brs, 2H), 7.00 (d, J = 7Hz, 1H), 7.55 (d, J = 10 H z, 1 H), 8.12 (d, J = 13 H z, 1 H), 8.7.5 (s, 1 H)

 (Example 95)

 1 — (3 — Amino 4-fluoro 6 — Methinolephenyl) — 6 — Phenole 1 7 — Piperazino 1,4,4-hydro So — 1, 8 — Naphthyridine 1 3 — Force oleic acid:

1 1 (3 — Amino 4 — Fnoreo Mouth 6 — Metinole Feninole) 1 7 — Chloro 6 — Phenolero 1, 4-Dihydro 14 So 1, 8 — Naphthyridine 1 3 — Force using oleic acid In the same manner as in Example 92, the title compound was obtained.

 Properties: yellow-brown powder

 Melting point: 23 9 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.08 (s, 3H), 2.68 (brs, 4H), 3.48 (brs, 4H), 5.28 (brs, 2H), 6.77 (d , J = 8Hz, 1H), 7.09 (d, J = 12Hz, 1H), 8.11 (d, J = 14Hz, 1H), 8.5 5 (s, 1 H)

 (Example 96)

 1 — (3 — Amino 1, 2, 4 — Gifnoreo Lofeninore) 1 7-[(3 S) — 3 — (Honore Minore Amino) Pyrrolidine 1 1 1 1-6—Funoleo 1,4-oxohydro 1,4,4-Hydroxy 1,8—Naphthyridine 13-force oleic acid:

 1 — (3 — Amino 1, 2,4-difluorophenol) 1 7-[(3S) — 3 — Aminopyrrolidine 1 1-6 Fluoro 4- 1-oxo 1,4-dihydro 1,8-naphthyridine 13-Hydronic acid 210 mg, formic acid 40 mg to 600 mg of N, Ν — In addition to dimethyl honole amide, the mixture was stirred at 120 ° C for one hour. 8 ml of diisopropyl ether was added, stirred and allowed to stand, and the supernatant was removed by decantation. Then, 2 ml of ethanol was added, and the mixture was heated under reflux for 20 minutes, allowed to cool, and the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, 180 mg The title compound was obtained.

Properties: light brown powder Melting point: 2 1 4-2 1 6

¹ HNMR (d ₆ -DMS 0) δ;

 1.83 (m, 1 1), 2.09 (m, 1Η), 4.36 (m, 1Η), 5.36 (s, 1Η), 6.96 (t , J = 8 Η ,, 1 Η), 7.36 (t, J = 10 Η ,, 1 Η), 7.96 (d, J = 4 Η ,, 1 Η), 8.07 (d, J = 13 3, 1Η), 8.38 (m, 1Η), 8.70 (s, 1Η)

 (Reference Example 6)

 Technology 8 — Chlorine 6, 7 — Diphnoreo Mouth 1 — (2, 4 — Gifnoreo lofeninole) 1, 4-Dihydro 1 4 — Okisoki Norin 1 3 — Carboxylate:

 Ethanol 3 — chloro-2,4,5 — Trifnoreo benzoyl acetate 5 g 3.9 g of orthoformic acid ethyl acetate, acetic anhydride 5 In addition to 5 g, the mixture was heated under reflux for 3 hours. After standing to cool, the mixture was concentrated under reduced pressure, and 20 ml of black hole foam was added to the residue. Under ice cooling, 2.3 ml of 2,4-difluoroaniline was added dropwise. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, hexane was added to the residue, the solid was collected by filtration, and ethyl 2- (3—chloro-2,4,5,6—tetrafluoronore I got a 3-(2,4-diphnoreoloamino) acrylate. This technology

2 — (3 — Chlores 2, 4, 5, 5 and 6 — Tetra nooreo べ ゾ ゾ () 3 — (2, 4 — Diphnoreo loamino) 2.5 g of potassium carbonate and 20 ml of N, N-dimethylformamide were added to 6.3 g of the mixture, and the mixture was heated and stirred at 90 ° C for 1 hour. After cooling, the reaction solution was poured into ice water, and the precipitate was collected by filtration and washed with water. The precipitate was dissolved in a black hole and washed with water. After drying over magnesium sulfate, the mixture was concentrated under reduced pressure, getyl ether was added to the residue, the solid was collected by filtration, and washed with ethanol and getyl ether to obtain 5.1 lg of the title compound.

 Properties: colorless powder

 Melting point: 2 1 1 — 2 12 ° C

 1 HNMR (CDC13) δ;

 1.40 (t, J = 7Η, 3Η), 4.40 (q, J = 7Hz, 2Η), 7.02-7.12 (m, 2Η), 7.44 (m, 1 Η), 8.3 1-8.3.3 7 (m, 1 Η), 8.3 3 (s, 1 Η)

 (Reference Example 7)

 Technology 5, 6, 7, 8 — Tetrafoloreno 1 — (2,4-diphenyl phenyl) 1 1, 4 — Dihydro 1 4 oxoki Norin 1 3 — Power Box Rate:

 The title compound was obtained in the same manner as in Reference Example 6, except that ethenore 2, 3, 4, 5, 5 and 6-pentafeno benzoyl acetate were used.

Properties: colorless powder

Melting point: 1 7 2-17 3 ° C

¹ HNMR (CDC 13) δ;

1.38 (t, J = 7 7, 3Η), 4.37 (q, J = 7Η, 2 2), 7.08 (m, 2Η), 7.50 ( m, 1 Η), 8.18 (s, 1 Η) (Reference Example 8)

 N — Ethoxy boninole 2, 4 — Difluorom — Phenylenamine methane olefonate:

 To 500 ml of concentrated sulfuric acid, 151 g of 2,4-difluorobenzoic acid was added, and 114 g of nitric acid powder was added little by little over 30 minutes while stirring with ice cooling. If stirring was continued for one hour, precipitates were formed in a shearlet form. This was added to 1.51 ice water, stirred for 30 minutes, and the precipitate was collected by filtration, washed with distilled water, air-dried, and dried over phosphorus pentoxide under reduced pressure. 5 g of 2,4-difluoro-5-nitrobenzoic acid

B got it

2,4—Difluoro—5—Nitrobenzoic acid 6.1 in addition to the dichloromethane of 201111, ogizarine norechloride 3 m 1, N, N—Dimethylholmami After adding 4 drops of the solvent and stirring for 2 hours, the solvent and excess reagent were distilled off under reduced pressure. The residue was dissolved in 6 ml of dichloromethane, and 2.1 g of sodium azide was added to 5 ml of N, N-dimethylformamide and stirred under ice-cooling. Dropped while it was. After stirring for 10 minutes and then returning to room temperature and stirring for 5 minutes, add 45 ml of ethyl ether, 15 ml of n-hexane and 100 ml of distilled water and shake. The liquid was separated. The organic layer was washed with 100 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Two-thirds of the residue was separated, 6 ml of ethanol was added, and the mixture was heated in a water bath at 80 ° C for 2 hours to obtain crude N-ethoxyquinone. 2,4-Difluorophenol 5—Dinitroaniline in ethanol solution Obtained.

 Add 14 ml ethanol to the above solution, add 2.0 g methansulfonate, 0.2 g 10% ethanol. Hydrogen was added overnight (15 hours) at room temperature with the addition of radium carbon. Since there was a precipitate, 20 ml of methanol was added thereto, and the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure, and the precipitated flaky crystals were collected by filtration and washed with a mixed solution of ethanol and diisopropenyl-1 to obtain 4.0 g of the title compound as slightly red crystals.

 (Reference Example 9)

 N — Phenol oleone boninole 2, 4 — Diphenole m — Phenylamine:

 2,4, -Diphnoleo 1-5 — Addition of 20.3 g of nitrobenzoic acid to 60 ml of dichloromethane, ogizarinolechloride 10 ml, N, N — dimethylol After adding 15 drops of muamide and stirring overnight, the solvent and excess reagent were distilled off under reduced pressure. The residue

Dissolve 30 ml of dichloromethane, add 15 ml of N, N-dimethylformamide, and stir while cooling under ice-cooling. 7.5 g were added in small portions. The mixture was stirred for 10 minutes, then returned to room temperature, stirred for 10 minutes, and then added with 100 ml of ethyl ether, 50 ml of n-hexane, and 400 ml of distilled water, and shaken. After that, the liquid was separated. The organic layer was washed twice with 400 ml of distilled water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. Add 12.0 g of benzyl alcohol, concentrate under reduced pressure, add 150 ml of toluene, heat in a 40 ° C water bath for 2 hours, and heat at 60 ° C. Heating in the bath for 25 hours, After heating in a hot water bath at 100 ° C for 1 hour, the mixture was concentrated under reduced pressure, and crude N-benzene was obtained as a slowly solidified residue. — Gifnoreo ro 5 — Nitro anilin.

 Add 84 g of iron powder to a mixture of 300 ml of distilled water and 200 ml of ethanol, and add 7 ml of concentrated hydrochloric acid little by little while stirring at 80 ° C. After the addition, the mixture was stirred for 5 minutes. Then, the total amount of the above N-pentanolone boninole2,4-diphenylolone 5-1-2-aniline is dissolved in 100 ml of ethanol. The mixture was added little by little to a gentle reflux, then 80. C 15 was stirred for 5 minutes. 500 ml of benzene was added and stirred for 5 minutes. The iron powder was separated by filtration, washed with ethanol, added with 200 ml of distilled water, and separated by shaking. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure through a short layer of silica gel powder. The precipitated colorless flaky crystals were dispersed in diisopropyl ether and collected by filtration to obtain 18.2 g of the title compound. (Example 9 7)

 Ethyl 8 — Black mouth 6, 7 — Diphnoreolor 11 (2,4-Diphnoreo mouth 5 — 2 Trofene 2) 1 1,4 1 Jihide mouth 4 1 ソ キ — 3 3 3 力 力 3 3 ： ：:

Echinore 8 — Black mouth 6, 7 — Giffnole 1 — (2, 4 — Giffnolero 1) 1 1, 4 — Jidro 4 — Oxo 2.5 g of quinoline 13-carboxylate was added to 15 ml of sulfuric acid, and under ice-cooling, 95 mg of nitric acid rim was added little by little, followed by stirring at room temperature overnight. Pour the reaction mixture into ice water and stir at room temperature. Stirred. The precipitate was collected by filtration and washed with water, ethanol, and getyl ether. 2.4 g of the title compound were obtained.

 Properties: colorless powder

 Melting point: 209-210 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7Η, 3Η), 4.40 (q, J = 7Η, 2Η), 7.43 (t, J = 9Η, 1Η) , 8.30 (s, 1 1), 8.36 (m, 2Η) [Example 98]

Ethyl 8 — Black mouth 6, 7 — Diffusion 1 — (2,4 1 Diffusion 5 — Honore Minore a Minofue 1 1, 4ジ 4 一 4 4 — — — — — — — — — — — — — — — — — — — — — — — — — — — — — 3 — 8 ク — — — ク — 8 Diphenyl chloro-5-Nitrophenyl) 1 1, 4 1 Dihydrochloride 1 4 1 oxoquinoline 1 3 — Power ureboki rate 2 g, 10% , ⁰ La di U beam di click carbon 2 0 O mg b b E data down 2 0 m 1, in addition to formic acid 1 0 ml, hydrogen stream under stirring for 3 hours at room temperature, the is added acetic anhydride al Stirred overnight. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. To the residue was added ethyl ether, and the solid was collected by filtration and washed with ethanol and getyl ether to obtain 1.9 g of the title compound.

Properties: yellow powder

Melting point: 2 23-22 9 ° C

_{'HNMR (d 6 - DMSO)} δ;

1.2 7 (t, J = 7 H z, 3 H), 4.2 3 (q, J = 7Hz, 2H), 7.76 (t, J = 10Hz, 1H), 8.23 (t, J = 10Hz, 1H), 8.33 (s, 1 H), 8.47-8.60 (m, 1 H), 8.5 1 (S, 1 H)

 (Example 9 9)

 1 — (3 — Amino 1, 4, 6 — diphenyl phenyl) 1 8 1 Chlorine 6, 7 — diphno 1, 4 — dihydro 1 4 — ォKIZO KINOLINE LINE 3 — Power

 Technology 8 — Chlor 6, 7 — Difluoro 11 (2, 4 — Gif Noreo 1 5 — Honore Minore A Minofue 1 1, 4 — Di 1.8 g of hydro-4-hydroxyquinoline was added to 5 ml of hydrochloric acid and 20 ml of acetic acid, and the mixture was refluxed for 3 hours. After allowing to cool, the mixture was concentrated under reduced pressure, ethanol was added to the residue, and the solid was collected by filtration and washed with ethyl ether. 1.4 g of the title compound were obtained.

Properties: light yellow powder

Melting point: 2 2 5 — 2 26.5 ° C

'HNMR (d ₆ — DMSO) δ;

 7.09 (t, J = 8 Η ζ, 1 Η), 7.43 (t, J = 11 Η Η, 1 Η), 8.40 (t, J = 9 Η ζ, 1 Η) ), 8.69 (s, 1Η)

 (Example 100)

No. 5—Penzinoleonix 1— (3—Ethoxycarbonyl Bonole Amino 1,4, 6—Difzoleo Mouth Feninole) 1,6,7—Diphnoleo Rows 1 and 4 —Jihdro 4 —Okisokinoline 1 3 One-way boxing:

 Addition of 1.35 g of ethynole 2-pentanorexoxy 3,4,6-trifluoromethyl benzoyl acetate to 860 mg of ethyl formate and 1.2 g of acetic anhydride The mixture was heated and stirred for 4 hours. After cooling, the reaction solution was concentrated under reduced pressure. To the residue was added 20 ml of black mouth holme, and under ice-cooling, N-ethoxyvinyl 2,4 of Reference Example 8 was added. A solution of 1.2 g of dimethylamine snorfonate and 0.5 ml of triethylamine in 20 ml of methanol was added dropwise. After completion of the dropwise addition, the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, 63 mg of potassium carbonate and 5 ml of N, N-dimethylformamide were added to the residue, and the mixture was heated with stirring at 90 ° C for 1 hour. . After allowing to cool, the reaction solution was added to ice water, the precipitated solid was collected by filtration, and this solid was dissolved in a clog port. The organic layer was separated. After drying over magnesium sulfate, the solvent was distilled off. Ethanol and getyl ether were added to the residue, and the solid was collected by filtration and washed with diethyl ether. 1.2 g of the title compound were obtained.

Properties: yellow powder

Melting point: 130-134 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.3 3 (t, J = 7 Η, 3), 1.3 8 (t,

J = 7 Η Η, 3)), 4.26 (q, J = 7 Η ζ,

2), 4.38 (q, J = 7 Η, 2), 5.

3 2 (s, 2 2), 6.41 (m, 1Η), 6.97 (d, J = 3Hz, lH), 7.19 (dd, J = 9 Hz, 10 Hz, 1 H), 7, 26-7.42 (m, 3 H), 7.64 (m, 2 H), 8.25 (s, 1 H) , 8.38 (t, J = 8 Hz, 1 H)

 (Example 10 1)

 1-(3-amino 4, 6-diphenyl phenyl) 1, 6, 7-diphenyl 5-hydroxy 1 1, 4-dihydro 4- Oxoquinoline 3 — Power of acid:

 Ethyl 5—Penzinoleone 1 1 1 (3—Ethoxyboninole Amino 4,6—Diphenyleole) 1 6,7—Diphneole Oro 1,4-dihydro-1-41-oxo quinoline 1-3-force norboxylate 50 O mg to 48% hydrobromic acid 5 ml, acetic acid 5 ml The mixture was heated under reflux overnight. After allowing to cool, the mixture was concentrated under reduced pressure, ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 130 mg of the title compound were obtained.

Properties: light yellow powder

Melting point:〉 270 ° C

'HNMR (d ₆ -DMS 0) δ;

 6.64 (dd, J = 6Hz, 12Hz 1H), 6.99 (dd, 8Hz, 9Hz, 1H), 7.49 (dd, 10H) z, 1 1 H z, 1 H), 8.77 7 (s,

1H)

 (Example 10 2)

Ethyl 1 — (3—Penzinole Okino Poninore Amino 4 and 6—Difluorene) 1 6 and 7—Difluoro 1 5— Memories 1, 4-1-1-4-1- Canole box:

 Ethanol 2 — Methylenol 1,3,4,6 — Trifnoreo benzobenzoyl acetate 2.6 g Orthoethyl formate 2.2 mg, Acetic anhydride 3 The mixture was heated and stirred for 2 hours. After cooling, the reaction solution was concentrated under reduced pressure. To the residue was added 20 ml of a black hole mouth, and under ice-cooling, N-benzyloxy 2-4 of Reference Example 9 was added. A solution of 2.78 g of dimethylamine in 1 O ml of chloroform was added dropwise. After completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and to the residue were added 1.65 g of carbonated lithium and 10 ml of N, N-dimethyl honoleum amide, and the mixture was heated and stirred at 90 ° C for 1 hour. did. After cooling, the reaction solution was added to ice water, and the precipitated solid was collected by filtration. This solid was dissolved in chloroform, the organic layer was separated, dried over magnesium sulfate, and the solvent was distilled off. Ethanol and ethyl ether were added to the residue, and the solid was collected by filtration and washed with getyl ether to obtain 2.4 g of the title compound.

Properties: yellow powder

Melting point: 202-204 ° C

¹ HNMR (CDC 13) δ;

 1.38 (t, J = 7 Hz, 3 H), 2.92 (d,

J = 3Hz, 3H), 4.38 (q, J = 7Hz, 2H), 5.21 (s, 2H), 6.50 (t, J = 9Hz , 1H), 7.08 (brs, 1H), 7.19 (t, J = 10Hz, 1H), 7.39 (brs, 5H), 8.27 ( s, 1 H), 8.38 (t, J = 8 H z, 1 H)

 (Example 10 3)

 1-(3-amino 4, 6-difluorophenyl) 1-6, 7-difluoro-5-methyl 1-1, 4-dihydro 4-oki Soquinoline 1 3 — Force oleic acid:

 Nozzle 1 — [3 — (Penzinoreokibonboninoreamimino 1-4, 6 — Difnoreo Lofenizore)] — 6,7 — Difnoreo mouth — 5 — Memories 1, 4 ヒ 4 4 4 4 4 1 キ キ キ キ

3 g of carboxylic acid was added to 1 O ml of hydrochloric acid and 20 ml of acetic acid, and the mixture was heated under reflux for 3 hours. After cooling, the mixture was concentrated under reduced pressure, ethanol was added to the residue, and the solid was collected by filtration and washed with diethyl ether. 940 mg of the title compound were obtained.

Properties: colorless powder

Melting point:〉 270 ° C

_{'HNMR (d 6 - DMSO)} δ;

 2.86 (brs, 3H), 7.07 (t, J = 8Hz, 1H), 7.20 (m, 1H), 7.52 (t, J = 1 1 Hz, 1H), 8.8 1 (s, 1H) [Example 104]

 Technology 5, 6, 7, 8 — Tetora no Ore 11 (2,

4 — Difluoro 5 — Nitroguchi 4 1 1 4 1 Dihydro 4 1 Okisoki 3 4 3 — Power supply box rate:

Technology 5, 6, 7, 8 — Tetrahoneororo 11 (2, 4 — Gifnorreolofeninore) 1 1, 4 — Jihdroro 4 -oxo Quinolin — 3 — Examples using carboxylates are examples The title compound was obtained in the same manner as in 97.

Properties: colorless powder

 Melting point: 2 3 5-2 3 8 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.22 (t, J = 7 Hz, 3 H), 4.2 3 (q,

J = 7Hz, 2H), 8.15 (t, J = 10Hz, 1H), 8.54 (s, 1H), 8.95 (t, J = 8H z, 1 H)

 (Example 10 5)

 Technology 5, 6, 7, 8 — Tetrafluoro 1 — (2, 4 — Diphnoreo 1 5 — Honoré Minore Aminofen 1) 1, 4 ーDihydro 4 1-oxo-quinoline 1 3 — Power-release box: Ethanol 5, 6, 7, 8 — Tetra-nore-roll 1 — (2, 4 — 1-5, 2-Trophenyl) 1 1, 4-Dihydro 1-4-Oxoquinoline 3-Force Except for using a box The title compound was obtained in the same manner as in Example 98.

Properties: light brown powder

Melting point: 1 7 9-18 2 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.25 (t, J = 7 Hz, 3 H), 4.2 2 (q,

J = 7Hz, 2H), 7.78 (t, J = 10Hz, 1H), 8.34 (s, 1H), 8.44 (s, 1H), 8.5 5 (t, J = 8 Hz, 1 H)

 (Example 10 6)

Ethel 5 — Benzinore Amino 6, 7, 8 — Trif Noreo Mouth 1 1 1 (2, 4 — Gifnoreo Mouth 1 5 — Honore Minorea Minohue 2 1) 1,4-Dihydro 1 4 1 Power box:

 Technology 5, 6, 7, 8 — Tetranorelo 11 (2, 4 — Dihnorero 5 — Honore Minorea Minofe 2 11) 1, 4 — Di Hydro 4 — oxoquinoline _ 3 — ureoboxylate 800 mg, benzylamine 0.2 1 ml, anhydrous carbon dioxide 24 O mg was added to 30 ml of toluene, and the mixture was heated under reflux. After allowing to cool, the mixture was concentrated under reduced pressure, and the residue was added with black hole form and washed with water. After drying with magnesium sulfate, the solvent was distilled off, getyl ether was added to the residue, and the solid was collected by filtration and washed with getyl ether. 600 mg of the title compound were obtained. Properties: yellow powder

Melting point: 15 1-15 6 ° C

 'H N M R (de-D M S O) δ;

 1.24 (t, J = 7 7, 3Η), 4.19 (q, J = 7Η, 2Η), 4.66 (m, 2Η), 7.29 ( m, 2Η), 7.36 (s, 3Η), 7.73 (t, J = 11 1, 1 1), 8.33 (s, 2Η), 8.50 (t, J = 8 H z, 1 Η)

 (Example 10 7)

Technology 5 — Amino 1 6, 7, 8 — Trifnoreo 1 _ (2, 4 — Gif Noreo 1 5 — Honoré Minorea 1 1, 4 — Dihydro 1 4 1 Okisokinoline 1 3 — Carboxylate: Echinore 5 — Penzinole Amino 1-6, 7, 8 — Trif Noreo 1-11 (2, 4 — Difluoro 1 5 — Honoré Minorea Minofue 2 Noré) 1, 4 — dihydro 4 1 oxoquinoline 1 3 — lipoxylate 600 mg, 10% palladium carbon 100 mg ethanol 2 The mixture was added to 0 ml and 10 ml of acetic acid, and stirred at room temperature for 2 days under a hydrogen stream. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Getyl ether was added to the residue, and the solid was collected by filtration and washed with getyl ether. 420 mg of the title compound were obtained.

Properties: yellow powder

Melting point:> 230 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 1.25 (t, J = 7Hz, 3H), 4.20 (q, J = 7Hz, 2H), 7.73 (t, J = 11Hz, 1H ), 7.88 (brs, 2 H), 8.30 (s,

1 H), 8.34 (s, 1 H), 8 49 (t, J = 8 Hz, 1 H)

 (Example 10 8)

 5 — Amino 1 11 (3 — Amino 4, 6 — Diphnoreolofenynore) 1, 6, 7, 8 — Trifnoreolo 1, 4 — Dihydro 1 4 — Oxoquinoline 1 3 — Power oleic acid:

Technology 5 — Amino 1 6, 7, 8 — Trifluoro 1 — (2, 4 — Gifnoreo 5 — Honomir Miramino 2 1) 1, 4-Hydroxy 4-oxoquinoline 1 3—The title compound was prepared in the same manner as in Example 99 except that oleoxycarbonyl was used. I got

Properties: yellow powder

Melting point> 270 ° C

_{'HNMR (d 6 - DMSO)} δ;

7.14 (t, J = 8 Hz, 1 H) ₍ 7.42 (t,

J = 10 Hz, 1 H), 8.50 (s, 1 H) (Example 109)

 Echinore 1 — (3—Penzinoleoxycarbonyl bonamino-4,6—Diphenylephenyl) 1—7—Cross mouth 1,4—Hydrogenー 4 1 oxo 1, 8 — naphthyridine 1 3 — carboxylate:

Echinole 2,6—Dichloronicotinoacetate 11.8 g was added to 8.8 ml of orthoformate and 13 ml of acetic anhydride, and the mixture was heated under reflux for 2 hours. did. The reaction solution was concentrated under reduced pressure. To 3.2 g of this compound was added 20 ml of toluene, and the N-benzyloxynanoboninole of Reference Example 9 was added to 2,4-diphenyleno-m-phenylene. Diamine 3. A solution of 10 ml of lg in toluene and 10 ml of ethanol was added dropwise, and after the addition was completed, the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and ethyl 2 — (2, 6 — dichloro nicotinole) 1-3 — (3 — benzo-amino-bonyl amine 4, 6 — Diphnore olofeninoreamino) A clear rate was obtained. The whole amount was dissolved in 10 ml of N, N-dimethylformamide, and 1.39 g of potassium carbonate was added. The mixture was stirred at room temperature overnight. The reaction solution was poured into ice water, the solid was collected by filtration, washed with ethanol and then with ethyl acetate, and 3.4 g of the title compound was obtained. I got

 Properties: colorless powder

 Melting point: 2 4 2 — 2 4 3 ° C

 1 HNMRR (CDC1a) δ;

 1.41 (t, J = 7Hz3H), 4.41 (q,

J = 7Hz, 2H), 5.22 (s, 2H), 7.01 (brs, 1H) 713 (t, J = 9Hz, 1H), 7.3 7 (s, 2H), 7.40 (s, 3H), 7.50 (m, 1H), 8.35 (m, 1H), 8.54 (s, 1H) ), 872 (d, J = 8Hz, 1H)

(Example 11)

 1 — (3 — Amino 4, 6 — Gif Noreolo Fennino) 1 7 1 Black mouth 1, 4-Dihydro 4 1 Oxo 1 1, 8 — Naf 1-Thyridine 1—force oleic acid:

 Ethyl 11 (3—Penzinolekishonoronboniramino 1-4, 6—Gifnole Orofeninor) 1 7 _Chlor 1,4—Jihid (B) 4-oxo-1,8-naphthyridine-13-canolepoxilate To 1.0 g, add 4 ml of 12N hydrochloric acid and 8 ml of acetic acid and heat for 3 hours Refluxed and stirred at room temperature overnight. The solid precipitated in the reaction solution was collected by filtration, and washed with ethanol, then with a cross-section film, and then with ethyl ether, to obtain 550 mg of the title compound.

Properties: colorless powder

Melting point:〉 270 ° C

_{'HNMR (d 6 - DMSO)} δ; 7.07 (t, J = 8Hz, 1H), 7.44 (t, J = 10Hz, 1H), 7.80 (d, J = 8Hz, 1H) ), 8.78 (d, J = 8 Hz, 1 H), 8.96 (s, 1 H)

 (Example 1 1 1)

 7 — Chromo 6 — Fluoro 1 — (4 — Fluorine mouth 1 3 — Nitro vinyl) 1, 4 — Dihydro 4 — Oxo 1 1, 8 — naphthyridine 1 3 — force oleic acid:

 7 — chloro 6 — phenol 1-(4 — phenyl) 1 1, 4-hydr 4 4 oxo 1 1, 8 — naphthyridge 1.5 g of sulfuric acid 1.5 g of concentrated sulfuric acid is added to 10 ml of concentrated sulfuric acid, and 1.4 g of potassium nitrate is added little by little, and heated and stirred at 80 ° C for 2 hours. did. After allowing to cool, the mixture was poured into ice water and stirred overnight. The precipitated solid was collected by filtration and washed with water, ethanol, and ethyl ether. 1.1 g of the title compound were obtained.

Properties: light yellow powder

Melting point:〉 270 ° C

'HNMR (d ₆ -DMS 0) δ;

 7.89 (t, J = 10 Η, 1), 8.09-8.17 (m, 1), 8.5 9-8.6 (m,

1), 8.80 (d, J = 7 Η, 1), 9.

0 8 (s, 1Η)

 (Example 1 1 2)

MECHNORET 7 — CHRORO 6 — HOLENO RO 1 – 1 (4 — HOLENO RO 3 – NITORI FUJINOLE) 1 1, 4 — JHYDRO 4 — OKI So 1, 8 — Naphthyridine 1 3 — Forced oleoboxate: Medium 2 夕 1 g of thionyl chloride was added dropwise to 5 m 1, and 7 ロ1 6 — Fluoro 1-11 (4 — Fluoro 3 — 2 Tro 2) 1 1, 4 — Dihydro 4 — Oxo 1, 8 — Naphtiri The mixture was added with 1.13 g of divinyl-3-carboxylic acid and heated under reflux overnight. After allowing to cool, the mixture was concentrated under reduced pressure. To the residue was added ethyl ether, and the solid was collected by filtration. 1.4 g of the title compound were obtained.

 Properties: yellow powder

 Melting point: 2 0 7 — 2 12 ° C

_{^{] HNMR (d 6 - DMSO)}} <5;

 3.78 (s, 3H), 7.87 (d, J = 9Hz, 1H), 8.10-8.17 (m, 1H), 8.54-18 . 6 2 (m, 2H), 8.78 (s, 1H) [Example 11]

 1-(3-Amino 1-4)-7-Black 1-4-1-4-Dihydro 1 4-Oxo 1 1, 8 — Naphthyridine 1 3 — Force oleic acid:

MECHNORET 7 — CROLOW 6 — FUNOREOL 1 – 1 (4 – FUNOLEO 3 – 2-TROFENYL) 1 – 1, 4 – HYDRO 4 – OZOSO 1, 8 — Naphthyridine 13 — Carboxylate 600 mg was dissolved in 30 ml of methanol, 10 ml of acetic acid, and 30 ml of dichloroethane. % 100 mg of palladium carbon was added. The mixture was stirred overnight at room temperature under a hydrogen atmosphere. The catalyst was removed by filtration with a membrane filter, and the filtrate was concentrated under reduced pressure. Acetic acid 4 m 1 in the residue, Hydrochloric acid (1 ml) was added, and the mixture was heated and stirred at 100 ° C overnight. The reaction solution was concentrated under reduced pressure, and ethyl ether was added to the residue. The solid was collected by filtration and washed with diethyl ether. 160 mg of the title compound was obtained.

Properties: light yellow powder

Melting point:〉 270 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 6.74-6.83 (m, 1H), 6.96 (dd,

J = 3 Hz, 8 Hz, 1 H), 7 2 3 (d d, J

= 9 Hz, 11 Hz, 1 H), 876 (d, J =

8 H z, 1 H) 8.79 (s, 1 H)

 (Example 1 1 4)

 Technology 7 — Chromo 1 — (3 — Ethoxy bonore Zoni Aminor 4,6-Gif レ レ ロ フ 6 — 1 6 — Fluoro 1 4 — Oxo 1, 1, 4 ー 1, 8 ナ Naphthyridine 1 3 力 力 ：

1.25 g of 2,6-dichloro-5-phenolic nicotine acetic acid ester ester prepared by conventional methods from 3-ethyl alcohol 1 2 — (2, 6 '-dichloro-5'-phenololenicotinol) A solution of methyl acrylate ester dissolved in methyl alcohol 1 At 0 m 1, refer to Reference Example 8 for N-ethoxycarbonyl 2, 4-fluorofluorom-phenyleneamine * methansulfonate 1.30 g of salt was added along with 500 mg of triethynoleamine. This solution was concentrated under reduced pressure. Add 50 ml of 50 ml of distilled water and shake with 50 ml of distilled water. Separation was performed later. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the residue were added 2.1 g of anhydrous sodium carbonate and 4 ml of N, N-dimethylformamide, and the mixture was stirred at 90 ° C for 15 minutes. After allowing the mixture to cool, 50 ml of black hole holme and 300 ml of distilled water were added thereto, and the mixture was separated.Then, the black hole form layer was washed twice with 300 ml of distilled water. After drying over anhydrous magnesium sulfate, the mixture was concentrated under reduced pressure. The precipitate was dispersed in ethanol, collected by filtration, and washed with ethanol and diisopropyl ether in that order to obtain 647 mg of the title compound.

 Properties: light brown powder

 Melting point: 209-211 ° C

'HNMR (d ₆ -DMS 0) δ;

 1.24 (t, J = 7 Hz, 3 H), 1.22 (t,

J = 7 Hz, 3 H), 4.13 (q, J = 7 Hz,

2 H), 4.24 (q, J = 7 Hz, 2 H), 7.

7 0 (t, J = 10 Hz, 1 H), 8 0 3 (t,

J = 8 H z, 1 H), 8.54 (d, = 8 ζ,,

1 H) ·, 8.76 (s, 1 H)

 (Example 1 1 5)

 7 — Chlorine 11 (3—Electrochemical) 4, 6—Diphenylelophenyl 1—6—Chlorine 4—oxo 1 1, 4 Dihydro 1, 8 — Naphthyridine 1 3 — Force oleonic acid:

Technology 7 — Chlorine 11 (3—Ethanol) Boninole Minor 4 and 6 — Giffnolero Lenyl 1 6—Fnolero 4 — Oxiso 1, 4-Hydro 1, 8 — Naphthyridine 1 — Carboxylate 200 mg 1.5 ml 3N hydrochloric acid and lml In addition to the acetic acid mixture, the mixture was heated under reflux for 3 hours and 40 minutes. The mixture was allowed to cool, the precipitate was collected by filtration, and washed with ethanol and diisopir-pirateether in that order to obtain 149 mg of the title compound.

Properties: light yellow powder

Melting point: 2 3 3-2 35 ° C

'HNMR (d ₆ — DMSO) δ;

 1.24 (t, J = 7 Hz, 3 H), 4.13 (q,

J = 7 Hz, 2 H), 7.71 (t, J = 10 Hz, 1 H), 8.08 (t, J = 8 Hz 1 H), 8.77 (d , J = 7 Hz, 1 H), 9.06 (s, 1H), 9.65 (s, 1H)

 (Example 1 16)

1 — (3 — Amino 1, 4, 6 — Gifnoreo Lofenyenor) 1 7 — Krollo 6 — Phorenoro 4 — Oxo 1, 4 — Jihidoro- 1, 8 — Naphthyridine — 3 — Separate synthesis of oleic acid: ethyl 7 — black 1 — (3 — ethoxycarbonyl-amino-4, 6-dihydro 1-6-dihydro 1, 4-dihydro 1, 8-naphthyridine 1 3-carboxylate Was added to a mixture of 2 ml of 6N hydrochloric acid and 2 ml of acetic acid, and the mixture was stirred and refluxed for 4 days. The mixture was allowed to cool, the precipitate was collected by filtration, the filtrate was concentrated under reduced pressure, 6 ml of 6 N hydrochloric acid was added to the residue, and the mixture was stirred and refluxed for 18 hours. Under reduced pressure Then, 1 ml of ethanol was added and the mixture was allowed to stand. The resulting precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order. The title compound was obtained as mg of pale yellow powder. (Example 1 1 7)

 7- (3—Aminoa zetidin-1 1-in-no-le) 1 1— (3—Amino-in 1,4,6—Gifno-re 1, 4 -Hydro 1 -Oxo 1, 8 -Naphthyridine 1 3 -Carbonic acid:

 1 — (3 — Amino 1, 4, 6 — Gifnoreo Lofeninor) 1 7 — Black Mouth 1 6 — Phoreno 1, 4 — Dihydro 4 — Oxo 1 1,8—Naphthyridin-1 3—Ponoroleic acid 3.7 g and 3—Aminoazetidin dihydrochloride 2.18 g and Triethylamine 6.06 g was added to 200 ml of acetonitrile. The mixture was stirred at 80 ° C for 15 hours. The solid generated after cooling was collected by filtration. Washing with ethanol and isopropyl ether gave 3.7 g of the title compound.

Properties: light yellow powder

Melting point: 168.5-170.5 ° C

1 HNMR (d ₆ — DMSO) δ;

 3.60-4.60 (m, 5H), 5.35 (brs, 2H), 6.95 (t, J = 8Hz, 1H), 7.35 (t , J = 10 Hz, 1 H), 8 0 3 (d,

J = 11.5 Hz, 1 H), 8.68 (s, 1 H) [Example 1 18]

1 — (3 — Amino 4, 6 — Gif Noreo Lofel) 1 6 ー Fluorine 7-(3-Hydroxyzidine 1 1-Innole) 1 1, 4-Hydro 4-Oxo 1 1, 8-Naphthyri Gin — 3 — Carbonic acid:

 1 — (3 — Amino 4, 6 — diphenyl phenyl) 1 7 1 Chlor 6 — Phenole 1, 4 — Dihydro 1 4 1 oxo 1, 8 — naphthyridine 1 3 — potassium oleic acid and 3 — hydroxyazetidin hydrochloride and triethylamine as in Example 1 17 To give the title compound.

Properties: light yellow powder

Melting point:〉 25 3 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 3.60-4.65 (m, 5H), 535 (brs, 2Η), 5.82 (brs, 1Η), 6.95 (t, J = 8Η, 1)), 7.35 (t, J = 10 Hz, 1 Η), 8.03 (d, J = ll. 5 Hz, 1 Η),

8.6.8 (s, 1H)

 (Example 1 1 9)

 1 — (3 — Amino 1, 4, 6 — Difluorovinyl) 1 6 — Fnoreo 1 7 — (3 — Methylaminoaminoazetidin 1 — 1 ) 1, 1-4-Hydroxy 4-1 oxo 1, 8-naphthyridine 1-3-oleic acid:

1 — (3 — Amino 1, 4, 6 — Gif Noreo Lo Feninoren) 1 7 1 Black mouth 1 6 — Fnoreo 1, 4-Dihydro 4 — Oxo — 1, 8 — Naphthyridine 1 3 — Force olevonic acid and 3 — Methylenaminominazetidine dihydrochloride and triethylamine The title compound was obtained in the same manner as in Example 11

Properties: colorless powder

 Melting point: 135.5-140.5 ° C

1 HNMR (d ₆ — DMSO) δ;

 2.53 (s, 3H), 3.80-490 (m, 5H), 5.38 (brs, 2H), 6.97 (t, J = 8Hz, 1 H), 7.36 (t, J = 10 0 H z,

1 H), 8.11 (d, J = 10.7 Hz, 1 H), 8.70 (s, 1 H)

 (Example 120)

 1 — (3 — Amino 1, 4, 6 — Gifnoreo Lofeninore) 1 7 — (3 — Etinorea Minoazetidin 1 1 inole) 1 6 — Fluoro Rows 1, 4 — Dihydro 1 4 1oxo 1, 8 — Naphthyridine 1 3 — Casolevonic acid:

 1 — (3 — Amino 4, 6 — Gif Norole Lofenenor) 1 7 1 Chrono 6 — Phenoole 1, 4-Dihydro 1 4 — Oxo — 1, 8 — Naphthyridine-1 3 — Force oleic acid and 3 — Ethynoleamino azetidin dihydrochloride and triethylamine, except that Example 11 was used. The title compound was obtained in the same manner as described above.

Properties: colorless powder

Melting point: 12.5-12.4 ° C

'HNMR (d ₆ — DMSO) δ;

0.98 (t, J = 7 Hz, 3 H) 2.4 5 (q, J = 7 Hz, 2 H), 3.2 0-4.8 0 (m, 5 H), 5 3 4 (brs, 2 H), 6.94 (t, J = 8 Hz, 1 H), 7.35 (t, J = 10Hz, 1H), 8.

0 1 (d, J = 10.7 Hz, 1H), 8.67 (s,

1H)

 (Example 1 2 1)

 1 1 (3—Amino 4 and 6—Difnoreo Lofeninole) 1 7 1 (3—Dimethylamino azetidine 1 1-innole) 1 6—F 1,4-Dihydro_4-1,4-oxo-1,8-Naphthyridin-13-Carbonic acid hydrochloride:

 1 — (3 — Amino 1, 4, 6 — Diphnoreolofenynore) 1 7 1 Black mouth 1 6 — Phonolero 1, 4 — Dihydro 1 4 — Oxo — 1,8—Naphthyridin-1 3—force oleic acid and 3—dimethylamino azetidin dihydrochloride and triethylamine were used except that Example 11 was used. In the same manner as 7, a free form of the title compound was obtained. 11 mg of this solid was dissolved in 5 ml of chloroform, and 2 ml of 4N hydrochloric acid / 1,41-dioxane was added. The solvent was distilled off, and 2 ml of ethanol was added to the residue. The generated solid was collected by filtration to obtain 6 O mg of the title compound.

Properties: light yellow powder

Melting point:〉 24 2 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 2.72 (s, hexagon), 3.90-4.80 (m,

5 H), 5.2 0-6 70 (br, 2 2), 7.18 (t, J = 8 Η ζ 1 Η), 7.45 (t, J = 10 Η, 1 Η), 8.13 (d, J = 11.1Η, 1Η), 8.73 (s1Η) (Example 1 2 2)

 1 1 (3—Amino 4 and 6—Gifnoreo Lofeninole) 1—6—Fnoreo 1— (Translation 1 2—Methylenol 3—Aminoaze 1,4-dihydro-1,4-dioxo-1,8-naphthyridin-1,3-potassic acid:

 1 1 (3-Amino 4, 6-diphenyl phenyl) 1 7-Black mouth 6-Fluoro 1, 4-Hydro 4-Oxo- 1, 8 — Naphthyridine 1 3 — Force oleic acid and trans 1 2 — Methinole 3 3 — Aminoazetidine dihydrochloride and triethyla Except that min was used, the title compound was obtained in the same manner as in Example 117.

Properties: light yellow powder

Melting point:> 2 3 7 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 0.90-1.35 (m, 3H), 3.20-3.

5 5 (m, 2 2), 3.80-4.60 (m, 2Η), 5.37 (brs, 2Η), 6.85-7.05 (m, 1Η) ), 7.25-7.50 (m, 1Η), 8.09 (d, J = 9Η, 1Η), 8.72 (s, 1Η) [Example 12 3]

 7-(3-Aminoazetidin 1 1-Innole) 1 1-(3-Amino 4, 6-Gifnore Orofenini) 1 6-Funoreo mouth 1,4-dihydro-1-41-oxo-1,8-naphthyridine-13-potassic acid ρ—toluenes-nolephonate:

Except for using the compound 117, the same as in Example 52, The title compound was obtained.

Properties: light red powder

Melting point: 1 7 9 — 1 8 4

'HNMR (d ₆ -DMS 0) δ;

 2.28 (s, 3 H), 3.50-4.80 (m,

5 H), 6.96 (t, J = 8 Hz, 1 H), 7.1 1 (d, J = 8 Hz, 1 H), 7.37 (t, J = 10 H z, 1H), 7.48 (d, J = 8Hz, 1H), 8.12 (d, J = 1.11Hz, 1H), 8.30 (brs, 3 H), 8.7 4 (s, 1 H)

(Example 1 2 4)

 7 — (3 — Aminoazetidin 1 1 — yl) 1 1 1 (3 — Amino 4, 6 — Gifnoreo Lofeninore) 1 6 — Fnoreo 1 , 4 — dihydro 4 1 -oxo 1, 8 — naphthyridine 1 3 — oleic acid methansulfonate:

 The title compound was obtained in the same manner as in Example 52 except for using compound 117 and methansulfonate. Properties: pale red powder Melting point:> 2 14 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 2.3 4 (s, 3 H), 3.80-4.80 (m,

5H), 6.96 (t, J = 8Hz, 1H), 7.37 (t, J = 10Hz, 1H), 8.14 (d, J = 1 1 2 Hz, 1 H), 8.31 (brs, 3 H), 8.74 (s, 1 H)

(Example 1 2 5) 7 — (3—Amino 3—Metinole 1-Thinine)-1— (3—Amino 4,6—Gifnoreo Lofenino) 1 6 — Phenoleuro 1, 4 -Hydroxy 4 oxo 1, 8 — Naphthyridine 1 3 —Carbonic acid:

 1 — (3 — Amino 4, 6 — Dih Norole Lofenyenor) 1 7 — Black 1 6 — Furoro 1, 4 — Dihydro 4 — Oxo — 1, 8 — Naphthyridine 1 3 — Potassium olevonic acid and 3 — Amino 3 — Methylazetidin dihydrochloride and triethylamine The title compound was obtained in the same manner as in Example 117. Properties: colorless powder

Melting point: 2 4 4 — 2 46.5 ° C

'HNMR (d ₆ — DMSO) δ;

 1.42 (s, 3H), 3.20-4.55 (m, 4H), 5.37 (brs, 2H), 6.95 (t, J = 8Hz) , 1 H), 7.36 (t, J = 10 Hz,

1 H), 8.07 (d, J = 1 1.1 Hz, 1 H), 8.7 1 (s, 1 H)

 (Example 1 2 6)

 7-(3-L-Alaninoreminoazetidin 1 1-Innole)-1-(3-Amino4, 6-Difnoreo Lofeninore) 1 6 — Phenole 1-, 4-dihydro 4- 4-oxo 1, 8 — naphthyridine 1 3 — Force oleic acid:

1 — (3 — Amino 4, 6 — Gif Noreolo Fennino) 1 7 — Black Mouth 6 — Fenolero 1, 4-Dihydro 1 4 — Oxo 1 1, 8 — naphthyridine 1 3 — oleic acid and 3 — L — ara The title compound was obtained in the same manner as in Example 117, except that nilaminoazetidine dihydrochloride and triethylamine were used. Properties: light yellow powder

Melting point: 208.5-2 I 4 V

1 HNMR (d ₆ --DMS 0) δ;

 1.28 (d, J = 6.8 Hz, 3H), 3.555-3.75 (m, 1H), 3.70-4.80 (m, 5H) , 5.38 (brs, 2H), 6.97 (t, J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H), 8.0 7 (d, J = 11.1 Hz, 1H),

8.70 (s, 1H), 9.07 (brs, 1H) [Example 127]

 1 — (3 — Amino 1, 4, 6 — Gif Norole Lofenyenor) 1 6 — Fulro 1 7 — (3 — L — Norinore aminoa zetidine 1 — 1, 4-dihydro 1-41-1, 1-8-naphthyridin-1-3-carboxylic acid:

 1 — (3 — Amino 1, 4, 6 — diphenyl phenyl) 1 7 1 Chlor 6 — Fluoro 1, 4 — Dihydro 1 4 — Oxo — 1, 8 — Naphthyridine 1 3 — Potassium olevonic acid and 3 — L — Phosphorinoleminoaminazetidine dihydrochloride and triethylamine The title compound was obtained in the same manner as in Example 117.

Properties: colorless powder

Melting point: 262.5-264.5 ° C

'HNMR (d ₆ -DMS 0) δ;

0.78 (d, J = 7Hz, 3H), 0.85 (d. J = 7 Hz, 3 H), 1.70-1.95 (m, 1 H), 2.91 (d, J = 5.5 Hz, 1 H), 3.70- 4.80 (m, 5H), 5.35 (brs, 2H), 6.95 (t, J = 8Hz, 1H), 7.35 (t, J = 10 Hz, 1H), 8.06 (d, J = 11.1 Hz, 1H), 8.52 (brs, 1H), 8.69 (s, 1H)

 (Example 1 2 8)

 1 — (3 — Amino 4, 6 — Giffnole oropheninole) 1 — 6 — Fnole ore 7 — (3 — Methinole aminopyrosine 1 — 1) 4-oxo-1,4, -dihydro-1,8-naphthyridine-1-3-force boronic acid:

 The title compound was obtained in the same manner as in Example 48 except that 3-methylaminopyrrolidin dihydrochloride was used.

Properties: colorless powder

Melting point: 2 73-2 76 ° C (decomposition)

'HNMR (d ₆ — DMSO) δ;

 1.79 (m, 1Η), 1.93 (m 1 H), 2.24 (s, 3H), 5.35 (brs 2 H), 6.96 (t, J = 8 Hz, 1 H), 7.36 (t, J = 10 Hz, 1 H), 8.03 (d, J = 12 Hz, 1 H), 8.68 ( s, 1 H)

 (Example 1 2 9)

1 — (3-Amino 1, 4, 6 — Gifnole or Lofenenor) 1-6 (North) 1 7 — [(3S) 1 3 — (Metinole) B Rigidine 1 1 — Indone 4 1-oxo 1, 4-Dihydro 1, 8 — Naphthyridin 1 3 — Forced oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that (3S) -13- (methylamino) pyrrolidine dihydrochloride was used. Properties: light brown powder

Melting point: 24 6-2 48 ° C (decomposition)

1 HNMR (d ₆ — DMSO) <5;

 1.79 (m, 1H), 1.92 (m, 1H), 2.23 (s, 3Η), 3.18 (m, 2Η), 5.35 (brs , 2Η), 6.97 (t, J = 8Η, 1Η), 7.36 (t, J = 10 0, 1Η), 8.02 (d, J = 1 (3 layers, 1 layer), 8.68 (s, 1 layer) (Example 13 0)

 1 — (3 — Amino 1, 4, 6 — Difnoreo lofenol) 1 6 — Folnorrero 7 — [(3 S) 1 3 — (Echnole amino) Gin-1 1-inole]-4-oxo 1, 4-dihydro 1, 8-naphthyridine 1 3-force

 The title compound was obtained in the same manner as in Example 48 except that (3S) -3- (ethylamino) pyrrolidine dihydrochloride was used. Properties: light brown powder

Melting point: 2 48-25 1 ° C (decomposition)

1 HNMR (d ₆ -DMS 0) δ;

0.98 (t, J = 7Η, 3Η), 1.75 (m, 1Η), 1.95 (m, 1Η), 5.35 (brs, 2Η), 6.96 (t, J = 8 Η, 1), 7. 36 (t, J = 11Hz, 1H), 8.01 (d, J = 12Hz, 1H), 8.67 (s, 1H) [Example 13 1 ]

 1 — (3 — Amino 1, 4, 6 — Diphenylenelofeninole) 1 7 1 (3 — Amino 3 — methyl pyrrolidine 11 1) 1 6 — Phenoleuro 4 1 oxo 1, 4 — Dihydro 1, 8 — Naphthyridine 1 3 — Power oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that 3-amino 3-methinolepyrrolidin dihydrochloride was used.

 Properties: colorless powder

Melting point: 2 23-22 5 ° C

¹ HNMR (d ₆ -DMS 0) <5;

 1.20 (d, J = 3Hz, 3H), 1.60 (m, 1st), 1.71 (m, 1st), 5.35 (brs, 2nd), 6.96 (t, J = 8 Hz, 1 H), 7.

36 (t, J = 10Hz, 1H), 7.99 (d, J = 13Hz, 1H), 8.63 (s, 1H) [Example 13 2 ]

 1 — (3 — Amino 4, 6 — Difluoro phenyl) 1 7 — (3 — Amino methyl pyrrolizin 1 1 1) 1 6 — Funol Oro 4 oxo 1, 1, 4 ヒ ヒ, 1, 8 ナ naphthyridine 1 3 — oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that 3-aminomethylpyrrolidinine dihydrochloride was used.

Properties: colorless powder Melting point: 205-210 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 1.42-1.988 (m, 2H), 2.60 (d, J = 7Hz, 2H), 5.34 (s, 2H), 6.96 (t , J = 8Hz, 1H), 7.35 (t, J = 10Hz, 1H), 8.01 (d, J = 12Hz, 1H), 8.6 6 (s, 1 H)

 (Example 13)

 1 — (3 — Amino 1 4, 6 — Gif Norole Lofenyen 1) 1 7 1 (4 — Amino Biperidine 1 1 — Inor) 1 6 — Funolero 4 1,4-Dihydro-1,8-naphthyridine 13-force carboxylic acid:

 The title compound was obtained in the same manner as in Example 48 except that 4-minopiperidine dihydrochloride was used.

Properties: colorless powder

Melting point: 2 1 2 — 2 15 ° C

1 HNMR (d ₆ -DMS 0) δ;

 1.28 (m, 2H), 1.74 (m, 2H), 2.95 (m, 1H), 3.10 (m, 2H), 4.06 (m , 2H), 5.39 (s, 2H), 6.97 (t, J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H) , 8.06 (d, J = 12Hz, 1H), 8.67 (s, 1H)

 (Example 13)

1 1 (3-Amino 4, 6-diphenyle) -(Sys 1 3-Amino 1-4-Methoxy pyridine 1-1) 1-6-Phloreo 1 and 4-Dihydro 4-1 Oxo 1 1,8-Naphthyridine-1 3—force oleic acid:

 The title compound was obtained in the same manner as in Example 48 except that cis-13-amino-4-methoxypyrrolidine was used.

 Properties: light yellow powder

 Melting point:〉 16 4 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 3.13 (s, 3H), 3.73 (m, 2Η), 3.93 (m, 1Η), 5.38 (brs, 2Η), 6.

9 7 (m, 1Η), 7.37 (m, 1Η), 8.10 (d, J = 12 2, 1 1), 8.71 (s, 1Η) Example 1 3 5]

 1 — (3 — Amino 4, 6 — Difnoreo lo phenyl) 1 6 — Funoreo 7 [7 — [3 — (2 — Hydroxeno oleno mino) Pyrrolidine] 1, 4 -Hydrogen 4 -oxo 1, 8 -naphthyridine 1 -force

 3— (2—Hydroxycinolenoamino) The title compound was obtained in the same manner as in Example 48 except that pyrrolidine dihydrochloride was used.

Properties: light yellow powder

Melting point:〉 2 35 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

1.65-2.13 (m, 2Η), 2.5 2-2.70 (m, 2Η), 3.42 — 3.58 (m, 2Η), 4.55-4.73 (m, 1H), 5.36 (brs, 2H), 6.97 (t, J = 8Hz, 1H), 7.36 (t , J = 1 1 Hz, 1 H), 8.04 (d, J = 1 3 Hz, 1 H), 8.69 (s, 1 H) [Example 13 36]

 1- (3—Amino 1-4, 6—Difluoropheninole) 1 7— (7—Amino 5—Azaspiro [2.4] Heptane 1 5 — Inole) 1 6 — Phenole 1-1, 4 — Dihydro 1-oxo-1, 8 — Naphthyridine 13 — Carbonic acid hydrochloride:

 7-tert-butylinolecanone boninole amino 5—azaspiro [2.4] heptane B form 17 3 mg, triethylamine 16 4 mg was added to 2 ml of dimethyl sulfoxide, and the mixture was heated and stirred at 80 ° C. 1-(3-amino4, 6-diphenololephenine) ) 1-7-Chromo 6-Fluoro 4-Oxo 1, 4-Hydro 1, 8-Naphthyridine 1 3-Potassium 20 O mg was added, and the mixture was stirred overnight. After cooling, getyl ether was added to the reaction solution, and the getyl ether layer was concentrated under reduced pressure. To the residue was added a black hole solution, washed with water, dried over magnesium sulfate, and the solvent was distilled off. Getyl ether was added to the residue, and the solid was collected by filtration. 30 ml of chloroform and 5 ml of 4N hydrochloric acid dioxane were added to this solid, and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, and diethyl ether was added to the residue. The solid was collected by filtration and washed with diethyl ether. 120 mg of the title compound were obtained.

Properties: yellow powder Melting point:〉 2 2 2 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 0.78 (m, 4H), 3.26-4.44 (m, 6H), 7.09 (m, 1H), 7.41 (m, 1H), 8 1 2 (d, J = 13 Hz, 1 H), 8.35 (brs, 3 H), 8.73 (s, 1 H)

 (Example 13)

 7- (3—Aminoazetidin-1 1-in-no-re) 1 6—Phoneole 1- (2,4—Di-no-re-o 1-5—Metinole 1), 4-dihydro-1-41,8-naphthyridine-13-force oleic acid:

 7 — Chromo 6 — Fluoro 1 — (2, 4 — Diffusion 1 5 — Methnole Aminofe 2 1) 1, 4 — Dihdro 4 — Example 11 except that oxo-1,8-naphthyridine-13-force olevonic acid, 3-aminoazetidin dihydrochloride and triethylamine were used. The title compound was obtained in the same manner as 7.

Properties: light yellow powder

Melting point:〉 23 1 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 2.69 (d, J = 4.3Hz, 3H), 3.80-14.80 (m, 5H), 5.83 (brs, 1H),

6.96 (t, J = 8Hz, 1H), 7.41 (t, J = 11Hz, 1H), 8.14 (d, J = 12Hz, 1 H), 8.20-8.60 (br, 2H), 8.

7 6 (s, 1H) (Example 1 3 8)

 7-[(3 S)-3-aminopyrroline 1 1-yl]-1-(3-Ethanol Poninole Amino 4, 6-Diffusion Enil) 1-6 — Fluoro 4 — oxo 1, 4 — dihydro 1, 8 — naphthyridine 1 3 — power oleonic acid:

 1-(3-ETOKONOREBONNORE NOMINO 4, 6-DIFFNOLE OLO FENINNORE) 1 7-CLOTH 1 6-FUNOREO 4-Oxo 1 1,4-Dihydro-1,8-Naphthyridine-13-Canoleponic acid 68 mg, (3S) -3: Aminopyrrolidine 70 mg It was added to 3501, N, N-dimethylformamide and stirred at 80 ° C for 20 minutes. Then, 0.5 ml of ethanol was added and the mixture was allowed to cool. The precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, and 73 mg of the title compound was obtained. I got Properties: colorless powder

Melting point:〉 280 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.23 (t, J = 7 7, 3Η), 1.34 (m, 1Η), 1.53-1.95 (m, 3Η), 2.42 (m ), 2.74 (m), 4.12 (q, J = 7Hz, 2Η), 7.63 (t, J = 10Hz, 1H), 7.

9 5 (t, J = 8 Η 1, 1 H), 9 9 9 (d, J = 7 Η ζ, 1 Η), 8.63 (s, 1 H)

 (Example 13 9)

7 — (3—Aminoazetidin) — 1—1 (3—Amino4, 6—Gifnoreo Lofeninole) 1-1, 4—Jihid Mouth 4 — Oxo 1, 8 — Naphthyridine 1 3 — Potassolevonic acid: 3 — Aminoazetidine dihydrochloride 6 lmg, N — Methyl vinyl mouth While stirring the 3 mg solution of 1 19 mg of acetonitrile at 80 ° C, 1-(3-amino4, 6-diphenol) 1 7 — Black mouth 1, 4 — Dihydro 1 4 — Oxor 1, 8 — Naphthyridine 1 3 — Power Norevonic acid Add 100 mg, 80 ° C For 2 hours and 50 minutes. After allowing the reaction mixture to cool, decantation was performed with getyl ether, a small amount of ethanol was added to disperse the solid, and the solid was collected by filtration. The solid was washed with ethanol and dimethyl ether in that order to obtain 63 mg of the title compound.

Properties: light yellow powder

Melting point:〉 240 ° C (decomposition)

'HNMR (d ₆ -DMS 0) <5;

 3.50-4.48 (br, 5H), 535 (brs,

2H), 6.73 (d, J = 9Hz 1H), 6.96 (t, J = 9Hz, 1H), 735 (t, J = 10Hz, 1 H), 8.32 (d J = 9 Hz, 1 H), 8.69 (s, 1 H)

 (Example 140)

 1 — (3 — Amino 1, 4, 6 — Difnoreo lofeninole) 1 7 1 [(3 S) 1 3 — Aminopyrrolidin 1 1 — yl] 1 1, 4 -Hydrogen 4 1-oxo 1, 8-naphthyridine 1 3 -force oleic acid:

Example 13 9 except that (3S) —3—aminopyrrolidine was used. The title compound was obtained in the same manner as described above.

Properties: light reddish brown powder

Melting point:〉 26 1 ° C (decomposition)

_{^{1 HNMR (d e - DMSO)}} δ;

 1.53-1.84 (m, 1H), 1884-2.15 (m, 1Η), 5.33 (brs, 2H), 6.82 (t, J = 10Hz, 1H), 697 (t, J = 8Hz, 1H), 7.35 (t, J = 10Hz,

1 H), 8.28 (d, J = 10 Hz, 1 H), 8.65 (s, 1 H)

 (Example 14 1)

 1 1 (3—Amino 1—6—Chloro—4—Fonolelo / Feninole) —7— (3—Aminoazetidin—1—Iinole)ー 1, 4 ー Hydro 1 4 — Oxo 1, 8 — Naphthyridine 3 — Power

 1-(3-Amino 1-6-Black mouth 1-4-Fluorophenyl)-1-7-Kuroh-6-Phenoole 1, 4-Hydro-1-4 The title compound was obtained in the same manner as in Example 13-39, except that oxo-1,8-naphthyridine-13-potassic acid was used.

Properties: light yellow powder

Melting point: 200-203 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

3.70-4.48 (br, 3H), 5.69 (brs, 2H), 6.96 (d, J = 8Hz, 1H), 7.46 (d , J = 12 Hz, 1 H), 8.04 (d, J = 12 Hz, H), 8.62 (s, H) [Example 14 2]

 1 — (3 _amino 6 — methyl 4 — phenolic)-7-(3 — aminoazetidin 1 1 1) 16-fluoro 1, 4-AGE HYDRO 4-1 oxo 1, 8-naphthyridine 1-3-oleic acid:

 1 1 (3 — Amino 1 6 — Mechinore 1 4 — Phenorero Feninore) 1 7 — Krollo 6 — Funoreo Mouth 1, 4 — Dihydro 1 4 — Oxo The title compound was obtained in the same manner as in Example 117 except that 1,8-naphthyridine-13-carboxylate was used.

Properties: light yellow powder

Melting point:> 2 38 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 1.82 (s, 3 3), 294-4.28 (br, 5Η), 5.27 (brs3H), 6.74 (d,

J = 9 Hz, 1 H), 7.09 (d, J = 12 Hz, 1 H), 8.09 (d, J = 10 Hz, 1 H), 8.52 (s, 1 H)

 (Example 14 3)

 1 — (3-Amino 1-4 -fluorophenyl) 1 7-[(3 S) 1 3-Aminopyrrolidin 1-1]-6 — Phenole 1 1, 4 — Dihydro-1-41,8 — Naphthyridin-3 — Power oleic acid:

1 — (3 — Amino 4 — Fnoreolo-Feninore) 1 7 — Krollo 6 — Phonorero 1, 4-Hidro 4 1-Oxo 1 1, 8-Naphthyridin 13-force oleonic acid, (3S)-3-aminopyrrolidinine, except that the title compound was obtained in the same manner as in Example 60. .

Properties: brown powder

Melting point: 26 2-26 5 ° C

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.56-1.83 (m, 1H), 1.86-2.09 (m, 1H), 5.50 (brs, 2H), 6.67-6. 7 8 (m, 1 H), 6.92 (d, J = 9 Hz, 1 H), 7.17 (t, J = 12 Hz, 1 H), 8.03 (d , J = 1 3 H z, 1 H), 8.5 3 (s, 1 H)

 (Example 1 4 4)

 1 1 (3—amino 4 — fluorophenyl) 1 7— [(3 S,

4 S) 1 3-Amino 4-Mesinol pyrrolidine 1 1-Innore]

— 6 — Funoleo Mouth 1, 4 — Dihydro 1 41 1 Kiso 1, 8

— Naphthyridine-1 3 — Force oleic acid:

 1 — (3 — Amino 4 — Fluoro-Feninole) 1 7 — Krollo 6 — Fluoro 1, 4 — Dihydro 1 4 1 1

8—Naphthyridine-13—force oleonic acid, (3S, 4S) -131 amino 41-methylpyrrolidine, the strength of Example 60 The title compound was obtained in the same manner.

Properties: brown powder

Melting point:> 270 ° C

'HNMR (d for DMSO) δ; 0.96 (d, J = 7 Hz, 3 H), 2.12 (brs, 1 H), 5.50 (s, 2 H), 6.68-6.76 (m , 1H), 6.89-7.01 (m, 1H), 7.19 (t, J = 11Hz, 1H), 8.03 (d, J = 13 H z, 1 H), 8.5 3 (s, 1 H)

(Example 1 4 5)

 1 — (3 — Amino 4, 6 — diphenyl phenyl) 1 7 1 (Sys 1 3 — Hydroxy 4 — Methyl phenol 1) 1-6—Finoleo mouth 1,4,4-Hydro-1-4—Oxoquinoline-1 3—Power oleic acid:

 1 — (3 — Amino 4, 6 — Gifnoreolofeninole) 1, 6, 7 — Gifnoreolo 1, 4 ー Gydrogen 4 — Oxoquinoline 1 The title compound was obtained in the same manner as in Example 60, except that 3-hydranoic acid and cis-3-hydroxy-14-meth-olefin were used.

Properties: brown powder

Melting point: 174-180 ° C

_{^{1 HNMR (d B - DMS 0}} ) δ;

 0.94 (d, J = 7Hz, 3H), 2.11 (m, 1H), 2.86-3.81 (m, 4H), 3.86

(m, 1H), 5.18 (brs, 2H), 5.93 (d, J = 6Hz, 1H), 7.04 (t, J = 8Hz,

1H), 7.50 (t, J = 10Hz, 1H), 7.86 (d, J = 13Hz, 1H), 8.62 (s1H) [ Example 1 4 6) 1 1 (3-Amino 1, 4, 6-Diphenylenelofeninole) 1 7 1 (Transform 1 3-Amino 4-methyl pyrrole resin 1 1 1 1-6—Funoleo Mouth 1, 4—Dihydro 1 4 1-year-old Kisoquinoline 1 3—Power oleic acid:

 1 — (3 — Amino 4, 6 — difluoronorphen) 1 6, 7 — difluoro 1, 4 — dihydro 41 monoquinoline — 3—Aminolenic acid, Trans- 1 3—Amino 4-methinolevione The title compound was obtained in the same manner as in Example 60 except that lysine dihydrochloride was used. .

Properties: light yellow powder

Melting point:〉 16 4 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.09 (d, J = 7Hz, 3H), 2.28 (m, 1Η), 2.97-3.91 (m, 5Η), 5.58 (brs , 2 Η), 5.96 (d, J = 7 Η,, 1 Η),

7.05 (t, J = 8 Η,, 1 Η), 7.52 (t, J = 10 Η ζ, 1 Η), 7.92 (d, J = 14 Η,, 1 Η), 8.6.6 (s 1 Η)

 (Example 1 4 7)

 1 — (3 — Amino 4, 6 — Diphenyl phenyl) 1 6-1 Fluoro 7 — [(3 S) — 3 — Methyl alumino pyridine 1 1-4-dihydro 4-oxoquinoline-3-carboxylic acid:

1 — (3-amino 1-4, 6 — diphenylophenyl) 1, 6, 7 — difluoro1, 4 — dihydro1 4-oxoquinoline The title compound was obtained in the same manner as in Example 60, except that -3—force oleonic acid and (3S) —3—methyl aminopyrrolidin were used.

 Properties: light yellow powder

 Melting point: 1 88-199 ° C

¹ HNMR (d ₆ — DMSO) δ;

 1.86 (brs, 1H), 200 (brs, 1H), 2.30 (s, 3H), 3.11-3.66 (m, 5H), 5, 5 4 (brs, 2H), 5.95 (d, J = 7Hz, 1H), 7.04 (t, J = 8Hz, 1H), 7.50 (t, J = 11 Hz, 1 H), 7.86 (d, J = 14, 1 H), 8.63 (s, 1 H) [Example 1 48]

 7-(3-Aminoazetidin 1 1-Innore) 1 1-(3-Amino 4, 6-Gifnore Oro Fenininore) 1 6-Funoreoroー 1, 4 — dihydro 1 4 — oxoquinoline 1 3 — power norebonic acid: 1 1 (3—amino 4, 6 — difluorophenyl) 1 6 , 7 — Difluoro 1, 4 — Dihydro 1-41-oxoquinoline — 3 — Potassic acid, 3 — Aminoazetidine dihydrochloride Otherwise in the same manner as in Example 60, the title compound was obtained.

Properties: colorless powder

Melting point:> 18 3 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

 3.76 (brs, 2H), 3.91 (m, 1H),

4.24 (brs, 2H), 5.55 (brs, 2H), 5.77 (d, J = 7Hz, 1H), 7.02 (t, J = 8Hz, 1H), 7.50 (t, J = 10H, 1H), 7.88 (d, J = 12Hz, 1H), 8.64 (s, 1H)

 (Example 14 9)

 1 — (3 — Amino 1, 4, 6 — diphenyl phenyl) 1 7 1 (trans 1 3 — amino 4-hydroxy pyridine) 1 1) 1 6, 8 — difluoride 1, 4-dihydro 4 — oxoquinoline 3 — power oleic acid:

 1 — (3 — Amino 4, 6 — Diphenylophenyl) 1, 6, 7, 8 — Trifnoreolor 1, 4-Dihydro 4 — Oxoquino The same procedures as in Example 60 were carried out except that phosphorus 13-casolebonic acid and trans 13-amino-3-hydroxypyrrolidin dihydrochloride were used. To give the title compound.

Properties: brown powder

Melting point:> 145 ° C (decomposition)

'HNMR (d ₆ — DMSO) δ;

 3.92-4.26 (m, 4H), 5.46 (brs, 2H), 7.10 (t, J = 9Hz, 1H), 7.40 (t , J = ll H z, 1 H), 7.86 (d,

J = 14 Hz, 1 H), 8.52 (s, 1 H) [Example 150]

7 — (3—Aminoazetidin) 1 1 1 (3—Amino 4 and 6—Gifnoreo Lofeninole) 1 6 and 8—Gifnore Orro 1, 4 — Jihdro 4 _ Oxokinoline 1 3 — Power Boronic acid:

 1 — (3 — Amino 1-4, 6 — difluorophenyl) 1 6, 7, 8 — Trifnorole 1, 4 — Dihydro 4-oxoquino The title compound was obtained in the same manner as in Example 60 except that phosphorus 3-carboxylate and 3-amino azetidin dihydrochloride were used. Properties: colorless powder

 Melting point:〉 203 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 3.90 (m, 1H), 4.10 (m, 1H), 4.49 (m, 2H), 5.46 (brs, 2H), 7.08 (t , J = 9Hz, 1H), 7.39 (t, J = 10Hz, 1H), 7.81 (d, J = 13Hz, 1H), 8.4 8 (s, 1H)

 (Example 15 1)

 1-(3-amino 4, 6-difluorophenyl) 1 6, 8-difluoro 1 7-(3-hydroxyazetidin 1-1 Nore) 1,4-dihydro-1-41-oxoquinoline-1-3—force

 1 — (3 — Amino 1, 4, 6 — diphenylophenyl) 1, 6, 7, 8 — Trifnoreolor 1, 4-dihydro 4 — oxoquino The title compound was obtained in the same manner as in Example 60, except that phosphoric acid, 3-carboxylic acid and 3-hydroxyazetidine hydrochloride were used.

Properties: colorless powder

Melting point: 2 18-22 5 ° C ¹ HNMR (d ₆ -DMS 0) δ;

 4.13 (brs, 2H), 4.50 (brs, 3H), 5.44 (brs, 2H), 5.72 (brs, 1H), 7.08 (t , J = 8 Hz, 1 H), 7.39 (t, J = 10 Hz, 1 H), 7.79 (d, J = 13 Hz,

1 H), 8.46 (s, 1 H)

 (Example 15 2)

 7- (3—Aminoazetidin) 1 1— (3—Amino 1,4,6—Gifnole Orofeninore) 1—8—Black mouth 6-Funoleo Mouth 1,4 -Hydroxy 4 -Oxoquinoline 13

 1 — (3 — Amino 4, 6 — Gifnolerofenenor) 1 8 — Chlorine 6, 7 — Gifnoleorro 1, 4-Jihiro 1 4 — The title compound was obtained in the same manner as in Example 60 except that oxoquinoline 13-potassolevonic acid and 3-amino azetidin dihydrochloride were used.

Properties: light yellow powder

Melting point:〉 270 ° C

'HNMR (d ₆ — DMSO) δ;

 3.75 (m, 1 H), 4.10 (m 2 H), 4.

6 6 (m, 2 H), 5.43 (brs 2 H), 6.97 (t, J = 8Hz, 1H), 7.36 (t, J = llHz, 1 H), 7.87 (d, J = 14 Hz, 1 H), 8.44 (s, 1 H)

(Example 15 3) 1 — (3 — Amino 1, 4, 6 — Difnoreo Lofenini) 1 7 1 [(3 S) — 3 — Aminopyrrolidin 1 — 1] 1 8 — Chromo 6 — Fluoro 1, 4 — Dihydro 4 — Oxoquinoline 1 3 — Carbonic acid:

 1-(3-Amino 4, 6-Diphnoreolofenenole) 1-8-Chloro 6, 7-Diphnolero 1, 4-Dihydro 1 4-O The title compound was obtained in the same manner as in Example 60 except that oxoquinoline 13-potassolenic acid and (3S) -3'-aminopyrrolidine were used. .

Properties: light yellow powder

Melting point:〉 205 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 1.17 (m, 1H), 2.09 (m, 1H), 3.02-3.81 (m, 5H), 5.41 (brs, 2H), 6 9 7 (m, 1 H), 7.38 (t, J = 11 Hz, 1 H), 7.94 (d, J = 14 Hz, 1 H), 8.5 0 (s, 1 H)

 [Example 15 5]

 1 — (3 — Amino 1, 4, 6 — diphenyl phenyl) 1 8 1 Chlorine 6 — Phoreno 1 — 7 — (3 — Hydroxylazine 1 1, 1-4-Hydro 4-Oxoquinoline 1 3-Force oleic acid:

1-(3-Amino 1-4, 6-Diphnoreolofeninore) 1-8 1 Black mouth 6, 7-Difluoro 1, 4-Dihydro 1-4 1 o Kisoquinoline 3 — Potassium boronic acid, 3 — Hydroxyzec The title compound was obtained in the same manner as in Example 60 except that dihydrochloride was used.

Properties: light yellow powder

Melting point: 1 45-150

_{'HNMR (d 6 - DMSO)} <5;

 4.18 (brs, 2H), 447 (brs, 1H),

4.71 (brs, 2H), 541 (brs, 2H), 5.71 (d, J = 5Η, 1Η) 6.96 (t, J = 8Η, 1Η), 7.37 (t J = 10 Hz, 1Η), 7.88 (d, J = 14 Hz, 1Η), 8.

4 4 (s, 1 H)

 (Example 15 5)

 1-(3-Amino 4, 6-Diphenyl phenol) 1 8 1 Chromo 6-Fluoro 7-Piperadino 1, 4-Hydroー 4 oxo quinoline ー 3 — oleic acid:

 1 1 (3 — Amino 1, 4, 6 — Gifnoreo lophenyl) 1 8 1 Chromo 6, 7 — Gifollow 1, 4-Jihiro 1 4 1 The title compound was obtained in the same manner as in Example 60, except that oxoquinoline-3—potassic acid and pyrazine were used.

Properties: light yellow powder

Melting point:〉 23 2 ° C (decomposition)

_{^{1 HNMR (d 6 - DMSO)}} δ;

 2.87 (brs, 4H), 319 (brs, 4 r),

5.4.3 (b rs, 2 H), 697 (t, J = 8 Hz,

H), 7.37 (t, J = ll Hz, 1H), 8 0 7 (d, J = 12Hz, 1H), 8.54 (s, 1H)

 (Example 15 6)

 1 1 (3—Amino 4 and 6—Difnoreo Lofenino) 1 7- (3—Amino 3—Methylene azetidine 1 1—Innole) 1 8 — Chromo 6 — Fluoro 1, 4-Hydro 4 — Oxoquinoline 1 3 — Power acid:

 1 — (3 — Amino 4, 6 — Gif Noreolo Fennino) 1 8 1 Chloro 6, 7 — Gif Norero 1, 4 — Jihdroro 4 — A The title compound was obtained in the same manner as in Example 117 except that oxoquinoline 13-force oleic acid and 3-amino-3-methylazetidine were used.

Properties: yellow powder

Melting point: 2 5 2 — 2 5 7

_{'HNMR (d s - DMSO)} δ;

 1.35 (s, 3H), 4.17 (brs, 2H), 4.30 (brs, 2H), 5.42 (brs, 2H), 6.96 (t , J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H), 7.87 (d, J = 14Hz, 1H), 8.4 3 (s, 1 H)

 (Example 15 7)

1 1 (3—Amino 1-4, 6—Diphenylene) 1 18 1 Chlorine 6—Phenylo mouth 7— (3—Metanolamine 1 1, 4 -Hydroxy 1 4 -oxoquinoline 1 3 1 1 (3—Amino 4 and 6—Gifnoreo Lofeninore) 1 8 1 Black mouth 1 and 6 and 7—Gifle low 1 and 4—Dihydro 4— The title compound was obtained in the same manner as in Example 11-17, except that oxoquinoline-3—force oleonic acid and 3—methinoleamino azetidine were used. .

Properties: light yellow powder

 Point: 2 2 0-2 24 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 2.20 (s, 3H), 3.45 (brs, 1H), 4.12 (brs, 2H), 4.63 (brs, 2H),

5.42 (brs, 2H), 6.96 (t, J = 8Hz, 1H), 7.36 (t, J = 10Hz, 1H), 7.86 (d, J = 14Hz, 1H), 8.43 (s, 1H)

 (Example 15 8)

 1 — (3 — Amino 4, 6 — Difnoreo lophenyl) 1 8 — Black mouth 6 — Funoreo mouth 7 — (3, 5 — Dimethinole bipera Gino) 1, 1, 4, 1, 4, 1, 4, 1, 4, 1, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4,,,,,,,,,,,,, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4 for Forbiddenic acid:

 1 1 (3—Amino 4 and 6—Gifnoreo lo phenyl) 1 8 1 Chrono 6 and 7—Gifnore 1 and 4—Jihidro 1 4 1 The title compound was obtained in the same manner as in Example 11-17, except that oxoquinoline 13-force oleic acid and 2,6-dimethyl pyridine were used. .

Properties: light yellow powder Melting point:〉 270 ° C

'HNMR (d ₆ — DMSO) δ;

 0.96 (d, J = 6Hz, 6H), 2.80 (m, 2H), 2.91 (m, 2H), 3.08 (m, 2H), 5.4.3 (brs, 2H), 6.97 (t, J = 8Hz,

1H), 7.38 (t, J = 11Hz, 1H), 8.07 (d, J = 12Hz, 1H), 8.56 (s, 1H)

 (Example 15 9)

 7-(3-Aminoazetidin 1-1) 1 1-(3-Amino 4, 6-Difnoreo Lofeninor) 1 6-Phenolero 5 — Hydroxy 1, 4-Hydro 4 — Oxoquinoline — 3 — Carbonic acid:

 1 1 (3—amino4,6-diphenylphenol) 1-6,7—diphenylole 1—hydroxy 1,4-dihydro4— The title compound was obtained in the same manner as in Example 60, except that oxoquinoline 13-carbonic acid and 3-amino azetidinini hydrochloride were used.

Properties: light yellow powder

Melting point:> 26 2 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

3.75 — 4.02 (m, 3H), 4.24 (brs, 2Η), 5.25 (d, J = 7Η1H), 5.54 (brs, 2 Η), 6.98 (t J = 8 Hz, 1 Η), 7.49 (t, J = 10 Hz 1 H), 8. 4 8 (s, 1H)

 (Example 16)

 1 — (3 — Amino 1, 4 — Gifnoreolophenyl) 1 7 1 [(3 S) — 3 — Aminopyrrolidin 1 1 — Innore] — 6 — Fluoro mouth 1-5 — Hydroxy 1, 4 — Dihydro 4 -oxo quinoline 1 3 — Power boronic acid:

 1 — (3-amino 4, 6 — diphenyl phenol) 1 6, 7 — diphenyl 1 5 — hydroxy 1, 4 — dihydro 4 — The title compound was obtained in the same manner as in Example 60 except that oxoquinoline 13-force oleonic acid and (3S) -3'-aminopyrrolidine were used.

Properties: light yellow powder

Melting point:〉 2 3 7 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

 2.01 (m, 1H), 2.21 (m, 1H), 3.

3 4-4.97 (m, 5H), 5.46 (d, J = 7Hz, 1H), 6.98 (t, J = 8Hz, 1H), 7. 5 0 (t, J = 10 Hz, 1 H), 8.64 (s, 1 H)

 (Example 16 1)

 7 — (3-Aminoa zetidin-1-Innole) 1 1-(3-Aminoa4, 6-Gifnoreo Lofeninore) 1-6-Finole 1 — Methanol 1, 4 — Dihydro 4 — Oxokinoline 13 3

1 — (3 — Amino 4, 6 — Gif Noreo Lo Fe Ninole) 1 6, 7 — difluoro 5 — methylone 1, 4 — dihydro π? — 4-oxoquinoline 1 3 — carboxylic acid, 3 — amide The title compound was obtained in the same manner as in Example 60 except that dihydrochloride was used.

 Properties: light yellow powder

 Melting point:〉 270 ° C

_{'HNMR (d 6 - DMSO)} δ;

 2.75 (brs.3H), 390 (brs, 2H), 4.01 (brs, 1Η), 4 2 6 (brs, 2Η), 5.55 (brs, 2 Η), 565 (d J = 7Η, 1Η), 6.99 (t, = 8Hz, 1Η), 7.

4 9 (t, J = 11 Hz, 1 H), 8.5 9 (s, 1 H)

 [Example 16 2]

 1 1 (3—Amino 4 and 6—Difnoreo Lofenini) 1 7-[(3S) —3—Aminopyrrolidin 1 1—1 1— Phenolero 5 — Methyl 1, 4 — Dihydro 4 1-year-old Kisokiline 1 3 — Carbonic acid:

 1 1 (3—Amino 4, 6—Difnoreo Lofenino) 1 6, 7—Difsoleo Mouth 1 5—Metinole 1, 4—Dihydro—4—Voice The title compound was prepared in the same manner as in Example 60 except for the use of quinoquinoline 13-capronic acid and (3S)-3-aminobiline lysine. Obtained.

Properties: light brown powder

Melting point:〉 197 ° C (decomposition) _{^{1 HNMR (d 6 - DMSO)}} δ;

 1.68 (m, 1H), 1.96 (m, 1H), 3.01-3.65 (m, 5H), 5.53 (brs, 2H), 5 8 1 (d, J = 7 Hz, 1 H), 6.99 (t, J = 8 Hz, 1 H), 7.49 (t, J

= 1 1 Hz, 1 H), 8.55 (s, 1 H) [Example 163]

 5 — Amino 1 1 (3 — Amino 1 4, 6 — Gifnore Orofeninore) 1 7 — [(3S) 1 3 — Aminopyrrolidin 1 1 1, 4 — dihydro 1, 4 — dihydro 1 4 — oxoquinoline 1 3 — power

 5 — Amino 11 (3 — Amino 1, 4, 6-diphenylophenyl) 1, 6, 7, 8 — Trifluoro 1, 4 — dihydro — 4 — Oxoquinoline 13 — Force oleonic acid, (3S) — 3 — Aminopyrrolidin, except that the title compound was obtained in the same manner as in Example 60. Was.

Properties: light yellow powder

Melting point:〉 2 4 7 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 1.62 (m, 1H), 1.89 (m, 1H), 3.

2 2 (m, 1 H), 3.39-3.78 (m, 4 H), 5.38 (brs, 2 H), 7.02 (t, J = 8 Hz, 1 H), 7.23 (brs, 2H), 734 (t, J = 10Hz, 1H), 8.23 (s, 1H) [Example 164] 5—Amino 7— (3—Amino azetidin-one-in-no-re) —1— (3—Amino-one 4,6—Di-fino-leo-phenyl) 8 — difluoro 1, 4 — dihydro 4 monooxoquinoline — 3 — dicarboxylic acid:

 5 — Amino 1 — (3 — Amino 4, 6 — Diphnoreolofenyno) 1 6, 7, 8 — Trifnoreolo 1, 4 — Dihydro- The title compound was obtained in the same manner as in Example 60 except that 4-oxoquinoline 13-3-olenoic acid and 3-amino azetidin dihydrochloride were used. Was.

 Properties: yellow powder

 Melting point:〉 2 3 7 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 4.04 (brs, 1H), 428 (brs, 2H), 4.48 (brs, 2H), 541 (brs, 2H), 7.05 (t, J = 8 Η,, 1)), 7.30 (m, 1 Η), 8.25 (s, 1 Η)

 (Example 16 5)

 7 — (3 — Aminoa zetidin-1-Innore) 1 1-(3-Amino 6-Black 1-4 Fluoro 1, 4 -Hydrogen 4 -Oxoquinoline 3 -Power

1 — (3 — Amino 1 6 — Black mouth 4 — Fnoreo Lo Feninore) 1 6, 7 — Gif Noreo Lo 1, 4 — Jihydro 1 4 1 year old The title compound was obtained in the same manner as in Example 1339, except that phosphoric acid was used. Properties: light yellow powder

Melting point:〉 208 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 3.88-4.58 (br, 5H), 5.69 (d, J = 8Hz, 1H), 5.92 (brs, 2H),

7.08 (d, J = 8Hz, 1H), 7.59 (d, J = 10Hz, 1H), 7.93 (d, J = 13Hz, 1 H), 8.6 1 (s, 1 H)

 (Example 16)

 No. 7 — Chlorine 1 — (2,4,1-Dihydronore 1-5 — Honoreminoreaminoheno 2) 1—6—Horenoro1,4-Dihydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Separate synthesis of carboxylates:

 Technology 7 — Chromo 6 — Fluoro 1 1 (2, 4 — Gif 1) 4 — Nitro f 2 1 4 — Oxo 1 1, 4 — G Hydro 1,8 —Naphthyridine 13 —Powerboxylate 30.5 mg together with 400 mg of iron powder in 1.5 ml of formic acid The mixture was stirred at 80 ° C for 3 hours. After filtering off the insoluble matter through a cellite, the filtrate is concentrated under reduced pressure, and the precipitate is dispersed in ethanol and collected by filtration. Ethanol, diisopropyryl -Wash in order and obtain 295 mg of the title compound as a pale yellow powder.

(Reference Example 10)

N-(t—butoxycarbonyl) 1 2, 4 — difluoro — m— phenylamine: N- (t-butoxycanoleponyl) -2,4-diphenylol in the same manner as in Reference Example 8, except that t-butanol was used in place of ethanol. Mouth 1-5-Nitroaniline was obtained as colorless crystals.

 The 3.8 g of this was combined with 360 mg of 10% palladium carbon in 50 ml of methanol and hydrogenated at room temperature for 4 days. After the catalyst was filtered off, the solvent and the like were distilled off under reduced pressure, and the precipitate was dispersed in diisopropyl ether and collected by filtration to obtain 3.2 g of the title compound as pale brown crystals.

 [Reference Example 11]

 Technology 8 — Chromo 1 — (2 — Chromo 4 — Fluoro mouth 1 2) 1, 6 — Gif oleo mouth 1, 4- Oki Soki No Lin 3-Power

 2—Cro-guchi-1 4—The title compound was obtained in the same manner as in Reference Example 6, except that phenolinoaniline was used.

Properties: colorless powder

Melting point: 208-211 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7 7, 3Η), 4.40 (q J = 7Η, 2Η), 7.16-7.23 (m, 1Η)

7.3.4 (dd, J = 3Η, J = 8Η, 1Η)

7.48 (d d, J = 5 Η, J = 9 Η, 1)

8.2 7 (s, 1 Η), 8.35 (t, J = 9 ζ 1 Η)

[Reference Example 1 2] チ ロ レ 一 7---------------------------- 3 — Power box rate:

 4 Same as in Reference Example 6, except that 1

5 to give the title compound.

 Properties: colorless powder

 Melting point: 2 2 6 — 23 1 ° C

¹ HNMR (CDC 13) δ;

 1.39 (t, J = 7 7, 3Η), 4.39 (q, ιο J = 7Η, 2Η), 7.20—7.24 (m, 2Η) ,

 7.3 4 — 7.35 (m, 2Η), 8.34 (t, J = 9Hz, 1Η), 8.42 (s, 1Η) [Reference Example 13]

 Ethyl 8 — Black mouth 6, 7 — Diflation 1 — (4 — Full 2 — Methyl 2 1) 1, 4-1 4 — Oki-Soki-no-lin 3 — Power-saving box rate:

 The title compound was obtained in the same manner as in Reference Example 6 except for using 2-methyl-4-anioleoanilin.

 Properties: light yellow powder

20 Melting point: 180-182 ° C

¹ HNMR (CDC 1 a) δ;

 1.40 (t, J = 7Hz, 3H), 2.10 (s, 3H), 4.40 (q, J = 7Hz, 2H), 7.02 — 7.1 0 (m, 2H), 7.2 2-7.36

25 (m, 1 H), 8.3 1 (s, 1 H), 8.37 (t, J = 9 Hz, 1 H)

 (Reference Example 14)

 1 1 (2—Blo-mo 4—Normal) 1 8—Cro 6—7, 7—Diphnole 1—1,4—Dihydro 1—4 KIKI KINO LINE 1 3 — CARBOX RATE:

 The title compound was obtained in the same manner as in Reference Example 6 except that 2-Promo 4-phenolylaniline was used.

Properties: light yellow powder

Melting point: 1 8 3 — 18 8 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7 7, 3Η), 4.40 (q, J = 7Η, 2Η), 7.18-7.32 (m, 1Η), 7.48-7.55 (m, 2Η), 8.27 (s, 1Η), 8.36 (t, J = 9Η, 1Η) [Reference Example 15]

 Technology 1 — (2—Metro 1–4) Fluoro 6—7—Difluoro 6 and 7—Difluoro 1, 4—Dihydro 4 IKISOKINO LIN 3-CARBOX RATE:

 The title compound was obtained in the same manner as in Reference Example 6, except that 2-fluoromethoxyaniline was used.

Properties: colorless powder

Melting point: 240-24 (decomposition)

 1 HNMRR (CDC1a) δ;

1.40 (t, J = 7Hz, 3H), 3.77 (s, 3H), 4.39 (q, J = 7Hz, 2H), 6. 7 2-6.89 (m, 2H), 7.31 (dd, J = 6Hz, J = 9Hz, 1H), 8.30 (s, 1H), 8. 3 4 (t, J = 10 Hz, 1 H)

 (Reference Example 16)

 8 チ レ — — — — — — — — — — — — — — — — — — — — — — 8 — — — — — — 8. Okisokinorin 1 3

 The title compound was obtained in the same manner as in Reference Example 6 by using 4-chloro-2-phenylene.

Properties: colorless powder

Melting point: 159-160 ° C

¹ HNMR (CDC 13) δ;

 1.40 (t, J = 7Hz, 3H), 4.39 (q, J = 7Hz, 2H), 7.31-7.47 (m, 2H), 8.3 2 -8.40 (m, 2H)

 (Reference Example 17)

 Technology 8 — Chromo 6, 7 — Diphnoreo Mouth 11 (2, 4, 6 — Trif Norele Lofeninore) 1 1, 4 — Dihydro 4 — KINOKINO LIN 3-Power box:

 The title compound was obtained in the same manner as in Reference Example 6, except that 2,4,6—trifnoroleoloaniline was used.

Properties: light yellow powder

Melting point: 1 35-1 49 ° C (decomposition)

 'H NMR (CDC13) δ;

1.40 (t, J = 7 Hz, 3 H), 4.40 (q, J = 7 Hz, 2 H), 693 (t, J = 7 Hz,

1 H), 8.25 (s, H), 8.34 (t, J

= 1 0 H z, 1 H)

 (Reference Example 18)

 8 — □ □ D — 6 7 — Jifnore 1-11 (2,4,6—Trif Norele Lofenenore) 1 1, 4- Norin 1 3 — Power

 Echinore 8-Black mouth 6, 7-Gifuru low 1-(2, 4, 6-Trifnorre Orofeninore) 1 1, 4-Jihdro 4 1.2 g of oxoquinoline 13-carboxylate was added to 5 ml of concentrated hydrochloric acid and 1 ml of acetic acid, and the mixture was heated under reflux for 3 hours. After cooling, the precipitated solid was collected by filtration, and washed with ethanol and a jet ethanol. The title compound was obtained in an amount of 750 mg.

Properties: light red powder

Melting point:〉 15 8 ° C (decomposition)

'' HNMR (d ₆ — DMSO) <5

 7.60-7.72 (m, 2H), 8.41 (t, J = 9Hz, 1H), 9.01 (s, 1H) [Example 1667]

 1 1 (3—Amino 4 and 6—Diphenolelofeninole) 1 7- (Translation 1 3—Amino 1 2—Methyl azetidin 1 1 1 1-8-Black 1-6-1,4-Dihydro 4-1-1-1-Carbonic acid:

1 — (3 — Amino 1, 4, 6 — Diph Nore Oro Fennino) 1 8 1 Black mouth 1, 6, 7 — Diph Norelo 1, 4 — Dihydro 1 4 — The oxoquinoline-1 3—force oleonic acid and the trans-13—amino—2—force using methylazetidin were the same as in Example 11-17. To give the title compound.

Properties: brown powder

Melting point:> 2 11 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 1.38 (brs, 3H), 3.73-3.90 (m, 1H), 4.69-4.82 (m, 1Η), 4.82-4. 9 7 (m, 1Η), 5.32-5.48 (m, 1Η), 5.49 (s, 1Η), 6.70-7.59

(m, 2H), 7.94 (d, J = 14Hz, 1H), 8 · 48 (s, 1H)

 (Example 1 6 8)

 1 — (3 — Amino 1, 4, 6 — diphenylene phenyl) 1 7 1 (4-methinole biperazine 1-1 inore) 1 8 — kuroro 6 — Phenoleuro 1, 4 — Dihydro 1 4 — Oxo monoquinoline 13 — Carbonic acid:

 1 1 (3—Amino 4 and 6—Diphenylovinyl) 1 8—Black 1 and 6 and 7—Difined Low 1 and 4—Dihydro 4 1 The title compound was obtained in the same manner as in Example 117 except that oxoquinoline 13-force olevonic acid and 4-methyl benzoperazine were used.

Properties: yellow powder

Melting point: 198-205 ° C (decomposition)

! HNMR (de-DMSO) δ; 2.54 (s, 3H), 2.81 (brs, 4H), 3.42 (brs, 4H), 7.01 (t, J = 7Hz, 1H), 7.40 (t, J = 11 Hz, 1 H), 8.15 (d, J = 12 Hz, 1 H), 8.62 (s, 1 H)

 (Example 16 9)

 1 1 (3—Amino 4 and 6—Diphenylophenyl) 1 7-[(3S, 4R) 3—Amino 4-methylpyrrolidin 1 4 レ] — 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8.

 1 — (3 — Amino 1, 4, 6 — Diphnoreolofeninole) 1 8 — Chloro 6, 7 — Diphnoleo 1, 4 — Dihydro 4 — Oki Example 11: Sokinolin 13-Carbonic acid, (3S, 4R) 3—Amino 4—Methanorepyrrolidine The title compound was obtained in the same manner as described above.

Properties: yellow powder

Melting point: 170-179 ° C (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 0.95-1.11 (m, 3H), 1.88-2.09 (m, 1Η), 2.60-3.72 (m, 5Η), 5. 3 8 (s, 1 Η), 5.46 (s, 1 Η), 6.82-7.52 (m, 2 Η), 7.96 (d, J = 14 ζ, 1Η), 8.40 (brs, 1Η) (Example 17 0)

1 — (3 — Amino 4, 6 — Gif Norele Lofenyen) 1 7 1 [(3 R) — 3 — Aminopyrrolidine 1 1 yl] — 8 — Black mouth 1 6 — Phenore mouth 1, 4-Hydro 1 4 — Oxo One quinoline one 3 — Force oleic acid:

 1 1 (3—Amino 4 and 6—Diphenyl phenyl) 18 1 Chromo 6 and 7—Difin 1 and 4—Dihydro 4— The title compound was obtained in the same manner as in Example 11-17 except that oxoquinoline 13-potassolenic acid and (3R) -3'-aminopyrrolidine were used. .

Properties: brown powder

Melting point: 169-179 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 1.5 2-1.80 (m, 1 H), 1.8 4-2.07 (m, 1Η), 2.7 1-3.82 (m, 5Η), 5. 40 (brs, 2 2), 6.93 (m, 1Η), 7.36 (t, J = 10Hz, 1Η), 7.88 (d,

J = 14 Hz, 1 H), 8.40 (s, 1 H) [Example 1Ί1]

 1 1 (3—Amino 4 and 6—Diphenyl phenyl) 1 7— (3—Amino azetidin 1 1—Innole) 1 8—Chloro 6 -Phenol 1, 4-dihydro 4-1-oxo-1-quinoline 1-3-olenoic acid p-tri-norenoene sulfonate:

1 1 (3—Amino 1-4, 6—Diphenyl phenyl) 1 7- (3—Aminoazetidin 1—yl) 1—8—Black 1-6-phenol 1, 4-dihydro 1-4 oxo-quinoline 1-3-carboxylate 44 0 mg of N, N-dimethyl honolem Ami In addition to 0.5 ml of the compound (1), 191 mg of p-toluene-nosoleic acid monohydrate was added, and the mixture was stirred at room temperature. Diethyl ether was added to the reaction solution, and the supernatant was removed. Ethanol was added to the residue, and the solid was collected by filtration and washed with diethyl ether to obtain 340 mg of the title compound.

 Properties: yellow powder

 Melting point: 211-220 ° C (decomposition)

1 HNMR (d ₆ -DMS 0) δ;

 2.28 (s, 3 3), 4.04 (brs, 1H), 4.42 (brs, 2Η), 4.76 (brs, 2H),

6.99 (t, J = 8Hz, 1H), 7.11 (d, J = 7Hz, 2H), 7.37 (t, J = 11Hz, 1H) ), 7.48 (d, J = 8Hz, 2H), 7.94 (d, J = 15Hz, 1H), 8.33 (brs, 3H), 8. 4 4 (s, 1 H)

 [Example 1Ί2]

 1 — (3 — Amino 1, 6 — Difluorophenyl) 1 7 — (3 — Aminoazetidine 1 1 ノ inole) 1 8 — Chro ro 6 — Fluoro 1, 4 — Dihydro 4 — Oxo monoquinoline 13 — Potassium sulfonic acid metholenate:

 The title compound was obtained in the same manner as in Example 171, except that methansulfonate was used.

Properties: light yellow powder

Melting point: 180-190 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ; 2.35 (s, 3H), 4.04 (brs, 1H), 4.43 (brs, 2H), 4.75 (brs, 2H), 6.99 (t , J = 8Hz, 1H), 7.37 (t, J = 11Hz, 1H), 7.95 (d, J = 14Hz, 1H), 8.3 6 (brs, 3 H), 8.48 (s,

1H)

 (Example 17 3)

 Ethyl 8 — Black mouth 6, 7 — Difnoreo 1 — (2 — Black mouth 4 — Funole 1 — Nitrofe 2 1) 1, 4 — Jihi Dro 1 4 1 Oxokinoline 1 3 — Power box box: Ethno 8 8 — Black port 6, 7 — Difnoreo 1 1 (2 — Black port Example 9 Example 1-9-Example 4 Example 1-1------------------------------------------------------------------------------- The title compound was obtained in the same manner as 7.

Properties: brown powder

Melting point: 1997-201 ° C

'HNMR (d ₆ -DMS 0) δ;

 1.27 (t, J = 7Η, 3Η), 4.25 (q, J = 7Η, 2Η), 8.23-8.32 (m, 2Η), 8.55 (s, 1H), 8.94 (d, J = 7Hz,

1 Η)

 (Example 17 4)

1 — (3 — Amino 6 — Black Mouth 1 — 4-Norre L-phenyl) — 8 — Black Mouth 1, 6 — 7 4 1-oxo quinoline 1 3 — Force oleic acid: Ethyl 8 — Chromo 6, 7 — Di phenol 1 — (2 — cro 1 4 — Fluor 5 — Nitro fu 1 2, 1 — 4 Hydro 4 — Okisoki Linole 3 — Power 1

5 g and 2 g of iron were added to 5 ml of formic acid, and the mixture was heated and stirred at 60 for 2 hours. The insolubles were removed by filtration through a celite, and washed with formic acid and black hole form. The filtrate was concentrated under reduced pressure, ethanol was added to the residue, and the solid was collected by filtration and washed with getyl ether. 4 ml of concentrated hydrochloric acid and 4 ml of acetic acid were added to this solid, and the mixture was heated under reflux for 1 hour. After cooling, the precipitate was collected by filtration, and washed with ethanol and diethyl ether to obtain 970 mg of the title compound.

 Properties: light yellow powder

Melting point: 2 3 7 — 2 42 ° C

¹ HNMR (d ₆ — DMSO) δ;

 7.12 (d, J = 8Hz 1Η), 7.50 (d, J = 12Hz, 1H), 841 (t, J = 9Hz,

1 H), 8.60 (s,: H)

 [Example 1-5]

 7-(3-Aminoazetidin 1-1-Innole) 1-1 (3-Amino 1-6-Chloro 4-Difno Lenole Lo Feninore) 1-8-C Loro 6 — Phenole Mouth 1, 4-Dihydro 1 4 — Oxoquinoline 1 3 — Power

 8 — Black mouth 6, 7 — Gifnoreo 1 (3 — Amino

6-Black mouth-4-レ 4 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 In the same manner as in Example 117, the title compound was obtained. Properties: colorless powder

Melting point:> 265 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 3.70 (brs, 1H), 4.06 (brs, 2H), 4.67 (brs, 2H), 5.76 (s, 2H),

6.99 (d, J = 8Hz, 1H), 7.46 (d, J = 11Hz, 1H), 7.88 (d, J = 14Hz, 1 H), 8.48 (s, 1 H)

 (Example 17 6)

 1 — (3 — Amino 6 — Black mouth 4 — Fro-noreno-Lofeninole) — 7 — [(3 S) — 3 — Aminopyrroline 1 — 1-inole] ― 8 — Black mouth 1 6 — Fluoro 1, 4 — Dihydro 1 4 — Oxo 1 quinoline 1 3 — Power oleic acid:

 8 — Black mouth 6, 7 — Difnoreo mouth _ 1 1 (3 — Amino 6 — Chloro 4 1 Fluorofeninole) 1 1, 4 — Jihdro 1 4 — Oxoquinoline 1 3 — Force oleonic acid, (3S) — 3 — Aminopyrrolidin was used in the same manner as in Example 11-17. The title compound was obtained.

Properties: light yellow powder

Melting point:〉 195 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

1.5 2-1.74 (m, 1H), 1.9 1-2.15 (m, 1H), 2.71-3.80 (m, 5Η), 5. 7 5 (brs, 2Η), 6.99 (t, J = 8Η, 1H), 7.46 (t, J = llHz, 1H), 7. 9 2 (d, J = 14Hz, 1H), 8.35 (s, 1H)

 [Example 1-7]

 Technology 8 — Chlores 6, 7 — Diphnoreo 1-11 (4 — Phoreno 1 5 — Nitrofu 2 1) 1, 4 — Dihydro 1 4 — KIKI KINO LIN LINE 3-Power Box Rate:

 Ethyl 8 — Chromo 6, 7 — Diphnoleo 1-1 (4 — Phenore olo fenizole) 1, 4 — Dihydro 4 — oxoquino The title compound was obtained in the same manner as in Example 97, except that phosphorus 3-boxylate was used.

Properties: colorless powder

Melting point: 2 4 9 — 25 6 ° C

¹ HNMR (d ₆ — DMSO) δ;

 1.26 (t, J = 7Η, 3Η), 4.23 (q, J = 7Η, 2Η), 7.84 (t, J = 10 0, 1Η) ), 8.14-8.19 (m, 1st), 8.23 (t, J = 9th, 1st), 8.50 (s, 1st), 8.6.5 -8.6.8 (m, 1 Η)

 [Example 1-8]

 8 — Black mouth 6, 7 — Jifnoleo mouth 1 — (3 — Amino 1 4 — Funore o Lofenenore) 1 1, 4-Jihdro 1 41 Oxo Quinoline 1 3—force oleic acid:

Technology 8 — Black mouth 5, 6, 7 — Trif norelow 1 — (4 — Firenollow 5 — Nitrophenyl) 1 1, 4 1 4 Iokisokinorin 3 — I used a carboxile Otherwise in the same manner as in Example 17, the title compound was obtained.

Properties: colorless powder

Melting point: 2 3 8-2 4 3 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 6.74-6.89 (m, 1H), 6.95-7.

0 7 (m, 1 H), 7.2 1 (t, J = 8 Hz, 1 H), 8.40 (t, J = 9 Hz, 1 H), 8.56 (s, 1H)

 [Example 1-9]

 7-(3-Aminoazetidin 1-1-Nore) 1 1-(3-Amino 4-Fenole Lo Feninore) 1-8-Black 1-6-Full Oro 1, 4 -Hydroxy 1 -4 oxo 1 quinoline 1 3

 8 — Black mouth 6, 7 — Difnoreo ro 11 (3 — Amino 4 — Funorelo feninole) 1 1,4 — Dihydro 4 — Oxo quino The title compound was obtained in the same manner as in Example 117 except that phosphorus-3-carboxylic acid was used.

Properties: yellow powder

Melting point: 2 36-24 6 ° C (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 3.77 (brs, 1H), 4.12 (brs, 2Η),

4.66 (brs, 2 layers), 5.58 (s, 2 layers), 6.60-6.72 (m, 1 layer), 6.87 (d, J = 8 layers) , 1 Η), 7.16 (t, J = 10 Η ,, 1 Η), 7.87 (d, J = 14 Hz, 1 1), 8. 3 9 (s, 1 H)

 (Example 18)

 Technology 8 — Chlorine 6, 7 — Gifnoreo Law 1 — (4-Fhnoreo 1 2 — Mechnole 1 5 — 2 Trof 2) 1 1, 4 1 Jihi Dro 1 4 1 Okisokinorin 1 3-Power box: 1 8 (Cross opening 6, 7-Diphnoles 1 1-(2-Met) No. 4 — レ オ ロ 1 1 1, 4 1 1 4 4 4 4 ォ 一 一 3 3 — — 実 施The title compound was obtained in the same manner as in Example 97.

Properties: red powder

Melting point: 187-19-11 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7 Η, 3), 2.25 (s, 3), 4.2 0 (q, J = 7 Η, 2), 7.36 ( d, J = 1 1 Η 1, 1 Η), 8.11 (d, J = 7 Hz, 1)) 8.26 (s, 1 Η), 8.38 (t, J = 9 Η ζ, 1 Η)

 (Example 18 1)

 8 — Chlorine 6, 7 — Diphenol 1 — (3 — Amino 4 — Phenole 6) 1, 4 — Dihydro 4 — Oxoquinoline 1 3 — Power oleic acid:

Echinore 8 — Black mouth 6, 7 — Difnoreo mouth 1 — (4 — Hinore mouth 1 2 — Methanol 5 — Two trophone 2) 1 1, 4 The title compound was obtained in the same manner as in Example 174 except that draw 41-oxoquinone 13-carboxylate was used. Properties: colorless powder

Melting point: 2 25-230 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 1.89 (s, 3H), 7.00 (d, J = 8Hz, 1H), 7.16 (d, J = 12Hz, 1H), 8.

4 2 (t, J = 9 Hz, 1 H), 8.5 1 (s, 1 H) [Example 18 2]

 1 — (3 — Amino 4 — Phenole 6 — Methyl phenyl) — 7 — (3 — Aminoazetidine 1-1) 1 8 — Black Mouth — 6 — Phenole Mouth 1, 4-Dihydro 4 — Oxo monoquinoline 1 3 — Carbonic acid:

 8 — Chlorine 6, 7 — Gifnoreo Mouth 11 (3 — Amino 4 — Fluoro_6 — Methanol Fever 2) 1, 1-4 — 4 — Oxoquinoline — 3 — Capillic acid The title compound was obtained in the same manner as in Example 117 except that carboxylic acid was used.

Properties: brown powder

Melting point:〉 25 1 ° C (decomposition)

'HNMR (d ₆ -DMS 0) δ;

 1.88 (s, 3Η), 3.71 (brs, 1H), 4.06 (brs, 2Η), 4.65 (brs, 2Η),

5.38 (s, 2 2), 6.79 (d, J = 7Η, 1Η), 7.06 (d, J = 1 1Η, 1Η), 7.91 (d, J = 13 Η, 1 Η), 8.29 (s, 1))

(Example 18 3) 1 1 (2 — Blo-mo 4 — Fn oor o 5 — 2 Tro f o 2 o 1) 1 8 — Kro o 6 and 7 — Ji f o n o ro 1 and 4 1 Jihdro 4 1 ソ キ キ 3 3 3 3 力 力 3 ボ 力 ： 力 ： チ チ: 1 — Black mouth 6, 7 — Diphnore low 1, 4 — Dihdro 4 1 Oki quinoline 3 — Power box In the same manner as in Example 97, the title compound was obtained.

 Properties: brown powder

 Melting point: 205-214 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.27 (t, J = 7 7, 3Η), 4.25 (q, J = 7Η, 2Η), 8.2.7 (t, J = 9Η, 1Η) , 8.41 (d, J = 11 1, 1Η), 8.53 (s, 1Η), 8.91 (d, J = 8Η, 1Η) [Example 1 8 4)

 8 — Chromo 6, 7 — Difluoro 1 — (3 — Amino 6 — Bromo 4 — Zoleo mouth phenyl) 1 1, 4 — Dihydro — 4 — Oxoquinoline 3 — Power oleic acid:

 Ethyl 1-1 (2-Bromo 4-1 Fluoro-5-2 口 口 二 二 一) 1-8-Chromo 6, 7-ジ フ 1, 4-— The title compound was obtained in the same manner as in Example 117 except that Hydro 4-oxoquinoline 3 — carboxylate was used. Properties: light yellow powder

Melting point: 2 3 1-2 39 ° C

_{'HNMR (d 6 - DMSO)} δ; 7.14 (d, J = 9Hz, 1H), 7.58 (d, J = 11Hz, 1H), 8.43 (t, J = 9Hz, 1H) ), 8.58 (s, 1 H)

 (Example 18 5)

 7 — (3 — Aminoazetidin 1 1 — yl) 1 1 — (3 — Amino 1 6 — Bromo 4 — B mouth 1 6 — phenol 1, 4-hydra 1 4 — oxo 1 quinoline 1 3 — force oleic acid:

 8 — chloro 6, 7 — diphnoleo 1-1 (3-amino 6-bromo 4-fluorophenyl) 1, 1-4-dihydro The title compound was obtained in the same manner as in Example 117 except that 4-oxoquinoline-3-carboxylate was used.

Properties: light yellow powder

Melting point:〉 200 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 3.89 (brs, 1H), 4.27 (brs, 2H),

4.71 (brs, 2H), 5.81 (s, 2H), 7.03 (d, J = 8Hz, 1H), 7.55 (d, J = 1 1 Hz, 1H), 7.93 (d, J = 14Hz, 1H), 8.33 (s, 1H)

 (Example 18 6)

1-1 (2-methoxy 4-phenolic 5-nit mouth-phenol) 1 8-crochet 1-6, 7-diphenyl 1-4- Low 4-1-3-Carboxylate: Etch 1-1 (2-Mexoxy 4-4) 1 8 — Black mouth 1, 6, 7 — Diphnole 1, 4 — Dihydro 4 1 oxoquinoline — 3 — Example 9 except for using carboxylate The title compound was obtained in the same manner as 7.

 Properties: light yellow powder

 Melting point: 220-225 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.40 (t, J = 7Hz, 3H), 3.92 (s, 3H), 4.40 (q, J = 7Hz, 2H), 6.94 ( d, J = 12 Hz, 1 H), 8.2 1-8.30 (m, 1 H), 8.26 (s, 1 H), 8.34

(t, J = 9 Hz, 1 H)

 (Example 18 7)

 8 — Black mouth 6, 7 — Giffnole 1 1 (3 — Amino 6 — Methoxy 1 4 — Fenole o Lofeninole 1 1, 4 — Jihid Mouth 1 4 1-oxo quinoline 1 3 — Force oleic acid:

 Technology 1 — (2 — Methoxy 1 4 — Fluoro 5 — Two-way Mouth 1) 8 — Black 1, 6, 7 — Diphenyle 1, 4 The title compound was obtained in the same manner as in Example 174 except that Hydro 4-oxoquinoline 13-carboxylate was used.

Properties: light yellow powder

Melting point: 1 4 3-15 1 ° C

'HMR (d ₆ -DMSO) δ;

3.70 (s, 3H), 7.19-7.37 (m, 2H), 8.40 (t, J = 9Hz, 1H), 8. 5 6 (s, 1 H)

 (Example 18 8)

 1-(3-Amino 6-Methoxy 4-Fluorophenyl) 1 7-(3-Amino Azetidine 1-1-1)-8- Roller 6 — Phoreo Mouth 1,4,4-Hydro 4 1-oxo-quinoline 1 3 — Power oleic acid:

 8 — Black mouth _ 6, 7 — Gifnoreo 1-11 (3 — Amino 1 6 — Methoxy 4 — Hookleolo feninole) 1, 4 — Jihide mouth The title compound was obtained in the same manner as in Example 11-17 except for using 1- 4-oxoquinoline-3-carboxylic acid.

Properties: light yellow powder

Melting point: ＞ 2 4 4 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 3.68 (brs, 4H), 4.05 (brs, 2H), 4.65 (brs, 2H), 5.01 (s, 2H),

6.87 (brs, 1H), 7.09 (d, J = 12Hz, 1H), 7.86 (d, J = 14Hz, 1H), 8.29 (s, 1 H)

 (Example 18 9)

 1 1 (3—Penzinolekishonorboniniboninoamimino4, 6—GifnoreoroFeninore) 1 8—Chloro6, 7—Diphnoleolo -5-2 trol 1, 4-Jihdro 4 1 year old Kisoki Lin-3-Power box:

Example 3 2-4, 1, 5-Trifluoro 6-2-Trobenzoinorecetate Example 10 The title compound was obtained in the same manner as described above.

 Properties: brown powder

 Melting point: 2 3 3-2 41 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.38 (t, J = 7 Hz, 3 H), 4.38 (q,

J = 7Hz, 2H), 5.21 (s, 2H), 7.01-7.15 (m, 2H), 7.40 (s, 5H), 8. 32-8.40 (m, 1H), 8.36 (s, 1H)

 (Example 190)

 5 — Amino 1 1 (3 — Amino 1 4, 6 — Gifnole Orofenyinore) 1 8 — Black mouth 1 6, 7 — Gifnole 1, 4 — Dihydro 1-4 — oxoquinoline 1 3 — power

 1 – 3 (Penzinole Okinoka Boninore Amino 1 – 4, 6 – Gifnole Orofeninore) 1 – 8 – Krollo 6, 7 – J Fluoro-5-Nitro1,4-dihydro-1-4-oxoquinoline-3-Carboxylate was used in the same manner as in Example 174, except that carboxylate was used. The title compound was obtained.

Properties: yellow powder

Melting point:> 270. C

_{'HNMR (d 6 - DMSO)} δ;

 7.02 (t, J = 8Hz, 1H), 739 (t, J = 10Hz, 1H), 8.46 (s, 1H) [Example 191 ]

5 — Amino 1 1 1 (3 — Amino 4, 6 — Gif 1) 7-(3-Aminoazetidine 1-1)-18-1-8-Chlorine 6-Phenoleolone 1, 4-Dihydro 4-Oxo One quinoline one 3 — Force oleic acid:

 5 — Amino 1 — (3 — Amino 4, 6 — Gifnoreo lophenyl) 1 8 _ Black mouth 6, 7 — Gifnoreo mouth 1, 4 — Jihi Draw 4 — oxoquinoline 3 — Power The title compound was obtained in the same manner as in Example 117 except that oleic acid was used.

Properties: brown powder

Melting point:〉 229 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 3.98 (brs, 1H), 4.38 (brs, 2Η), 4.67 (brs, 2Η), 5.39 (s, 2Η), 6.90 (t , J = 8Η, 1Η), 7.34 (t, J = llHz ,, lH), 8.29 (s, 1Η) [Example 1992]

 Echinore 1 11 (3—Benji Loki Shika Nore Boni Nomina Minor 4, 5, 6—Trif Nore Talent Rofu 2 Nor) 1 8—Kuro Mouth 1 6, 7— Diphnorero; I, 4-dihydro-1-41-

 Technology 3 — chloro-2,4,5—trino-noreo benzo-norrea acetate, Ν—penzinoleoxysica noreboninore 4,5,6,1-trif-noreo The title compound was obtained in the same manner as in Example 102 except for the use of r-m-phenylenediamine.

1 HNMR (d ₆ -DMS 0) δ;

1.42 (t, J = 7Hz, 3H), 4.40 (q, = 7 H z, 2 H), 5.2 1 (s, 2 H), 7

0 5 (brs, 1H), 7.39 (s, 5H), 8

1 9 (brs, 1H), 8.31 (s, 1H), 8

3 4 (t, J = 8 Hz 1 H)

 (Example 19 3)

 1 — (3 — Amino 4, 5, 6 — Trif Norrero 1) 8 — Black 1, 6, 7 — Difnoreo 1, 4-Dihydro 4 — Oxoquinoline 1 — Power acid:

 Echinore 1 1 (3—Penzinolekishonoreboninoreminino 1-4,5,6—Trif-Nolero-Lofeninore) 18—Cross-mouth 1-6,7— Difluoro-1,4—dihydro-14-oxoquinoline-3—The title compound was prepared in the same manner as in Example 103 except that carboxylate was used. Obtained.

Properties: colorless powder

Melting point: 2 32-2 38 ° C

¹ HNMR (d ₆ — DMSO) δ;

 6.88 (dd, J = 4Hz, J = 9Hz, 1H), 8.40 (t, J = 9Hz, 1H), 8.79 (s, 1H)

 (Example 1 94)

 7-(3-Aminoa zetidin-1-1)-1-(3-Amino-4, 5, 6-Trif Noreo-Lofenini)-8- Rollo 6 — Fluoro 1, 4-Hydro 1 4 — Oxoquinoline 3 — Carbonic acid:

1 — (3 — Amino 4, 5, 6 — Trifnorolenophenyl) — 8 — chloro 6, 7 — diphtholene 1, 4-dihydro 4 — oxoquinoline 3 — Example 1 17 except that carboxylic acid was used The title compound was obtained in the same manner.

Properties: light yellow powder

Melting point:〉 2 2 4 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 3.73 (brs, 1H), 4.08 (brs, 2 r),

4.68 (brs, 2 2), 5.78 (s, 2Η), 6.78 (t, J = 6Η, 1Η), 7.87 (d, J-14 H z, 1 Η), 8.5 5 (s, 1 Η)

(Example 1 95)

 1- (3-tert-butoxy bonbonylamino-4, 6- di-no-noreo-lo-fen-in-no-) 1-8-bro-mo, 6--7-di Function 1, 4 — Dihydro _ 4 1 キ キ — — — — — — —

 Technology 3 — Bromo 2, 4, 5 — Trinole vent outlet zone acetate, reference example 10 N— (t—butoxy Nore) The title compound was obtained in the same manner as in Example 102 except that 1,2,4-diphenylole 1 m-phenylenediamine was used.

_{'HNMR (CDC 1 3) δ} ;

1.40 (t, J = 7Hz, 3H), 1.54 (s, 9 ，), 4.40 (q, J = 7Η, 2Η), 6.8 1 ( brs, 1Η), 7.07 (t, J = 10 0 Η, 1ζ), 8.25-8.48 (m, 2Η), 8.38 (S, 1Η) (Example 1 96)

 1-(3-Amino 1, 4-6-dihydro-1-4-6-7-diphnoleo 1-1, 4-dihydro 4- KIZO KINOLINE LINE 3 — Power

 1- (3-tert-buty-no-le-canon-bon-l-amino-4,6-di-f-nor-e-ro-f-en-in-o-) 1--8-b-mol- 6,7-di-f-nor-e-ro 1, 4-Dihydro 4-oxoquinoline 13-Other than using carboxylate, the title compound was prepared in the same manner as in Example 103. Obtained.

 Properties: yellow powder

 Melting point: 2 2 8 — 2 32 ° C

¹ HNMR (d ₆ — DMSO) δ;

 7.05 (t, J = 8 Η ,, 1 Η), 7.43 (t, J = 11 Η ,, 1 Η), 8.43 (t, J = 9 Η,, 1 Η) ), 8.69 (s, 1 word)

 (Example 1 97)

 7 — (3 — Aminoazetidin-1 1-in-no-le) 1 1 — (3 — Amino 1--4, 6 — difluoro-feninole) 1 8 — Blo-mo 1 6ー Fluorine mouth 1, 4 — dihydro 4 1 oxo 1 quinoline 1 3 — power oleic acid:

 1 — (3 — Amino 4, 6 — Gifnoorenofen) 1 8 Bloom 6, 7 — Gifnooréo 1, 4 — Jihiro 4 —Oxoquinolin-3—caproluconic acid The title compound was obtained in the same manner as in Example 117 except that carboxylic acid was used.

Properties: light yellow powder Melting point:> 206 ° C (decomposition)

_{'HNMR (d 6 - DMSO)} δ;

 3.76 (b rs, 1 H), 4.07 (b rs, 2 H),

4.68 (brs, 2H), 5.41 (s, 2H), 6.92 (t, J = 8Hz, 1H), 7.38 (t, J = 1 1 H z, 1 H), 7.90 (d, J = 14 H z, 1 H), 8.46 (s, 1 H)

 (Example 1 98)

 No. 1 1 [3 — (N — t — N シ カ ポ N N ー ー) 1, 4, 6 — フ ノ レ オ 8 8 8 8 8 クRolls 6 and 7 — Diphenyle 4 — Oxo 1 and 4 — Hydro 1 — 3 — Canole box:

1.40 g of 3—Cro mouth 1-2,4,5—Trifluoro mouth benzoyl acetate ethyl ester prepared by a conventional method 3—Ethoxy 1 2 — (3,1-chloro-2 ', 4 *, 5'-trifluoro-benzobenzoylene) Chloro-honolem with cinnamate dissolved In 10 ml of the solution, add N— (t—butoxycarbonyl), 4,6—diphenol-m—phenyleneamine to the end of the reaction by TLC. Added. This solution was concentrated under reduced pressure. To this was added 1.4 g of anhydrous potassium carbonate and 6 ml of N, N-dimethylaminophenol amide, and the mixture was stirred at 90 ° C for 10 minutes. After cooling, add 1.4 g of anhydrous calcium carbonate and 5.0 g of methyl iodide, and add 60. The mixture was stirred at C for 2 hours. Add 50 ml of black mouth hologram and 500 ml of distilled water to separate the solution. After washing twice with distilled water, the extract was dried over magnesium sulfate anhydride, concentrated under reduced pressure, added with 3 ml of ethanol and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order to give 1.38 g of the title compound.

 Properties: light yellow powder

 Melting point: 19 2 _ 19 4 ° C

 'H NMR (CDC1a) δ;

 1.43 (t, J = 7 7, 3Η), 1.44 (s, 9Η), 3.22 (s, 3Η), 4.41 (q, J = 7Η) ζ, 2 Η), 7.10 (t, J = 9 Η ζ, 1 Η),

7.38 (t, J = 8Η Η, 1 1), 8.34 (dd, J = 8, ,, 10 0 ,, 1Η), 8.58 (s, 1Η) [ Example 19 9)

 1 — (3 — methinorea 1, 4, 6 — diphnoreolophenyl) 1 8 — black 1 6, 7 — diphnoreo 1 4 1 oxo 1 1, 4 — di Hydroquinoline 1-3—force oleic acid:

 Ethyl 1-[3-(Ν-t-buty-carbon-loop-me-no-re-a-mino)-1, 4-6-diphenyl Mouth 6, 7-diphnoleo Mouth 4-oxo 1, 4-dihydroquinoline 13-carboxylate 1.26 g 4 ml of 4 ml In addition to a mixture of hydrochloric acid and acetic acid (1: 1, v / v), the mixture was stirred and refluxed for 1.5 hours. After adding 5 ml of distilled water and allowing to cool, the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, to obtain 890 mg of the title compound. .

Properties: light yellow powder Melting point: 2 1 7 — 220 ° C

¹ HNMR (d ₆ — DMSO) δ;

 2.67 (d, J = 5Hz, 3H), 5.95 (bs1H), 7.06 (t, J = 8Hz1H), 745 (dd, J = 1 0 H z, 1 2 H z 1 H), 8

4 1 (dd, J = 9Hz, 10Hz, 1H), 872 (S, 1H)

 (Example 200)

 7-(3-Aminoazetidine) 1 1-(3-Methylamine 1, 4-6-Difluorophenyl) 1-8-Chloro 6- Phenoleuronic acid 4 — oxo 1, 4-chlorohydroquinoline 13 monocarboxylic acid:

 1 — (3 — methinorea 1, 4, 6 — diphnolero feninole) 1 8 — chloro 6, 7 — difluoro 4 — oxo 1, 4 ジD-quinoline 13-force oleic acid 150 mg, 3-amino azetidin dihydrochloride 110 mg, N-methylpyrrolidin 25 O mg was added to 65 O mg of N, N-dimethyl honoleamide, and the mixture was stirred at 90 ° C for 1 hour. After adding 0.5 ml of ethanol, the mixture was allowed to cool, and the precipitate was collected by filtration, washed with ethanol and diisopropyl ether in that order, and added with 130 mg. The title compound was obtained.

Properties: colorless powder

Melting point: 209-212 ° C

¹ HNMR (d ₆ — DMSO) δ;

2.68 (d, J = 5Hz, 3H), 3.69 (m, 1 H), 4.02 (m, 2 H), 4.65 (m, 2 H), 5.89 (brs, 1 H), 6.96 (t, J = 8 Hz, 1 H), 7.40 (t, J = 10 Hz, 1 H), 7.88 (d, J = 14 Hz, 1 H), 8.48 (S, 1 H)

 (Example 201)

1 1 (3—Amino 4, 6—Gifnole Orofeninore) 1 6, 7—Gifnolero 8—Metxo 1 and 4—Jihid B 1 — oxo quinoline 1 3 — force output box: echino 2, 4, 5 — trif nore ro 3 — meth oxy benzene To 4.1 g of Tate, 8.6 ml of acetic anhydride and 3.2 ml of triethyl onoletoformate were added, and the mixture was heated under reflux for 2 hours.The solvent was distilled off, toluene was added to the residue, and toluene was added. Boiled. Apply 10 ml of chloroform to the residue, and add 0 ml. In C, N—Benzykoxy cane Boninore 1,2,4—Difluorom—Fenylenediamine 1.8 lg Cloth mouth Holm 10 ml The solution was added dropwise and stirred at room temperature for 3 days. The solvent obtained by evaporating the solvent of the reaction mixture was subjected to silica gel chromatography and eluted (elution solvent: ethyl acetate: hexane = 1: 8) to obtain an oily substance. 2. Add 180 mg of potassium carbonate to a 4 ml solution of 580 mg of N, N—dimethyl honoleamide in 4 g and at 100 ° C. Stirred for 25 minutes. The reaction solution was poured into ice water, ice water and ethyl acetate were added to the reaction solution, the organic layer was separated, washed with water, dried over magnesium sulfate, and the solvent was distilled off. Attached to silica gel chromatography chromatograph (elution solvent: black mouth form: methanol = 10: 1), The obtained solid was collected by filtration and washed with getyl ether to obtain 250 mg of the title compound.

Properties: light yellow powder

Melting point: 1 5 9 — 16 2 ° C

_{'HNMR (CDC 1 3) δ} ;

 1.39 (t, J = 7 7, 3Η), 3.57 (s, 3Η), 4.37 (q, J = 7Η, 2Η), 6.8.4 ( t, J = 8 Η ζ, 1 Η), 7.00 (t, J = 9 Η ,, 1 Η), 8.08 (t, J = 9 Η ζ, 1 Η), 8.26 (s, 1 Η)

 (Example 202)

 1 1 (3-Amino 1-4, 6-diphenylophenyl) 1 6, 7-diphenylo 8-methanol 1 1, 4-dihydro 1 4 1 KIZO KINOLINE LINE 3 — Power

 Technology 1 — (3 — Amino 4, 6 — Gifnorelophenyl) 1, 6, 7 — Gifnoreo 1 8 — Methoxy 1, 4 RO 4—oxoquinoline 13—The title compound was obtained in the same manner as in Example 103 except that carboxylate was used. Properties: colorless powder

Melting point:> 2 7 7 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

3.12 (s, 3 3), 6.71 (t, J = 9Hz, 1H), 7.00 (t, J = 10Hz, 1H), 7.73 (t, J = 9Hz, 1H), 8.20 (s, 1H) (Example 203) 7 — (3 — Aminoa zetidin 11 1) 1 1 — (3 — Amino 4, 6 — Difnoreo Lofeninor) 1 6 — Fenolero 8 — Methoxy 1 and 4 — Dihydro 1-41-oxoquinoline 13-hydroxy-rubic acid:

 1-(3-Amino 1, 4, 6-diphnorelo feninole) 1 6, 7-difuzoreo 1 8-methoxy 1, 4-dihydro 4 1 o Suspension of 1-Omg of oxoquinoline-l-carboxylic acid was suspended in 4 ml of diethyl ether, and 9 ml of boron trifluoride getyl ether complex was added under ice cooling. The mixture was stirred for 1.5 hours. Diethyl ether was added to the reaction solution, and the precipitated solid was collected by filtration and washed with ethanol and diethyl ether in that order to obtain a pale yellow powder.

 3 — 70 mg of amino azetidin dihydrochloride, 0.17 ml of triethylenamine, 1 ml of dimethinolecinolexamide 1 m The mixture was stirred at ° C, 100 mg of the above compound was added, and the mixture was stirred at the same temperature for 2 hours. Diethyl ether was added to the reaction mixture, and the mixture was decanted. 5 ml of 80% methanol and 5 ml of triethylamine were added to the residue, and the mixture was refluxed overnight, and ethanol was added to the reaction mixture. Was added and the solid was collected by filtration to obtain 34 mg of the title compound as a tan powder. Properties: yellow powder

Melting point:〉 290 ° C

¹ HNMR (d ₆ — DMS 〇) δ;

3.11 (s, 3H), 3.74-3.89 (m, 2H), 3.90-4.02 (m, 1H), 4.38 4 8 (m, 2H), 5.36 (brs, 2H), 7.14 (t, J = 9Hz, 1H), 7.30 (t, J = 10 Hz, 1 H), 7.76 (d, J = 12 Hz, 1 H), 8.39 (s, 1 H)

 (Example 204)

 8 — Black mouth 6, 7 — Difnoreo 1-1 (2,4,6-Trifluoro 3 — Nitrofu 2 1) 1, 4 — Dihydro 4 — oxoquinoline 1 3 — carboxylic acid:

 8 — Chromo 6, 7 — Giffnoré Low 1 — (2, 4, 6 — Trif Norele Lofeninore) 1 1, 4 — Jidroro 4 The title compound was obtained in the same manner as in Example 9 except that norin-3-carboxylic acid was used.

Properties: light yellow powder

Melting point: 15 7-15 9 ° C

'HNMR (d ₆ — DMSO) δ;

 8.16 (t, J = 11 1Η, 1Η), 8.40 (t, J = 9Hz, 1H), 9.0.6 (s, 1Η)

(Example 205)

Technology 8 — Chromo 6, 7 — Diphnoreo 1-11 (2, 4, 6 — Trifnoreo 1 3 — Nitroh 1 2) 1 1, 4 1 Jihi Draw 4—Okisoki Line 3—Power Output Box: 8—Crawls 6 and 7—Gifnore 1-11 (2, 4, 6— 1-, 4-dihydro- 1- 4,4-dihydro- 1- 4-oxoquinoline 13-to-force bonoboric acid (830 mg) 2 ml of thionyl chloride was added, and the mixture was stirred at 80 ° C overnight. After slowly adding dropwise 4 ml of ethanol to the reaction mixture under ice-cooling, the solvent of the reaction mixture was distilled off, and the precipitated solid was collected by filtration. I got

Properties: light yellow powder

Melting point: 1 6 7-16 9 ° C

¹ HNMR (CDC 13) δ;

 1.4 1 (t, J = 7 Hz 3 H), 4.4 1 (q,

J = 7Hz, 2H), 7.19 (t, J = 9Hz, 1H), 8.22 (s, 1H), 8.35 (t, J = 9Hz , 1 H)

 (Example 206)

 Echinore 8 — Black mouth 6, 7 — Gifnoré 1 — (2, 4, 6 — Trifnorre 3 — Honore Minore A Minofen 2) 1 1, 4 1

 Technology 8 — Chlores 6, 7 — Difluoro 1-11 (2, 4, 6 — Trifolone 1 3 — Nitrof 2 1) 1, 4 1 The title compound was obtained in the same manner as in Example 1666, except that dihydroxy 4-oxoquinoline 13-potassium oxylate was used. Properties: light brown powder

Melting point: 1997-199 ° C

 (Example 207)

 1-(3-Amino 2, 4, 6-Trif Norre Lo Fennino)-8-Chro Lo 6, 7-Dih No Lo Low 1, 4-Di Hidr 1 4 1 oxoquinoline 1 3 — Power oleic acid:

Technology 8 — Black mouth 6, 7 — Giffnole 11 (2, 4, 6 — Trifnoré mouth 3 3 — Honore milu aminofen 2) 1 The title compound was obtained in the same manner as in Example 19, except that 1,4-dihydro-1-oxoquinoline-3-potassium borosilicate was used.

Properties: light yellow powder

_{'HNMR (d 6 - DMSO)} δ;

 5.57 (brs, 2H), 7.42 (t, J = 11Hz, 1H), 8.40 (t, J = 9Hz, 1H), 8.91 (s, 1 H)

 (Example 208)

 7-(3-Aminoa zetidin-1-Innore) 1 1-(3-Amino 2, 4, 6-Trifnorre Orofeninore) 1-8-C Rollo 6 — Fluoro 1, 4-Hydro 4 — Oxoquinoline 1 3 — Carbonic acid:

 1-(3-Amino 2,4,6-Trifnoroleno Feninole) 1-8 -Chloro6,7-Difnoreolo 1,4 -Jihidero 4 The title compound was obtained in the same manner as in Example 117 except that oxoquinoline-3-3-carboxylate was used.

Properties: light brown powder

Melting point:〉 290 ° C

_{'HNMR (d 6 - DMSO)} δ;

3.77-3.86 (m, 1H), 4.15-4.27 (m, 2H), 4.64-4.75 (m, 1H), 5. 5 2 (brs, 2 H), 7.38 (t, J = 10 Hz, 1 H), 7.91 (d, J = 13 Hz, 1 H), 8.66 (s , 1 H) (Example 209)

 No. 1 — (3—Benzi-Loki-shibon-bonirami-no- 1-4, 6—Gifnoreo-lo-heninore) 16—Cro-mouth 17, 8—Difluoro Rows 1, 4,,,,,,,,,,,,,,,,,,,,,,, ロ

 Technology 5 — Black mouth 1, 2, 3, 4 — Trifnoreo mouth Benzo no acetate, 3 — Penzinole boninone 1 2, 4 ーThe title compound was obtained in the same manner as in Example 102 except for using diphenylol-m-phenylenediamine.

Properties: light yellow powder

Melting point: 204-205 ° C

 'H NMR (CDC13) δ;

 1.39 (t, J = 7Η, 3Η), 4.38 (q, J-7Η, 2Η), 7.02 (brs, 1Η), 7.11 ( t, J = 10 Hz, 1 Η), 7.39 (s,

5H), 8.28 (s, 1H), 8.35—8.50 (m, 2H)

 (Example 210)

 1 — (3 — Amino 4, 6 — Diph Noreolo Fennino) 1 6 1 Black 1 7, 8 — Diph Nore 1, 4-1 Oxoquinoline 1-3—force oleic acid:

No. 1 — (3—Penzinole okinore Boninore Amino 1-4, 6—Diph Norelo Lofeninore) 16—Cross mouth 17, 8—Diphnole Rows 1 and 4 — Dihydro 4- 1-oxoquinoline 13 — Same as in Example 103 except that carboxylate was used. To give the title compound.

Properties: colorless powder

Melting point: 2 7 6-2 7 8 ° C

_{'HNMR (d 6 - DMSO)} δ;

 7.15 (t, J = 9 Hz, 1 H), 7.45 (t,

J = 11 Hz, 1H), 8.38 (d, J = 8Hz, 1H), 8.73 (s, 1H)

 (Example 2 1 1)

 1 1 (3—Amino 1, 4 and 6—Gifnoreo Lofenini) 1 7-[(3S) —3—Amino pyrrolidine 1—1] —6— Black mouth 1 8 — Fluoro 1, 4 — Dihydro 4-oxoquinoline 3 — Power oleic acid:

 1 — (3 — Amino 1, 4, 6-diphenyl phenyl) 1-6 1-7, 8-diphthol low 1, 4-dihydro 1-4 The title compound was obtained in the same manner as in Example 60 except that oxoquinoline 13-potassic acid was used.

Properties: light yellow powder

Melting point:〉 240 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

 1.5 1-1.68 (m, 1H), 1.8 8-2.

0 4 (m, 1H), 5.44 (brs, 2H), 7.09 (t, J = 8Hz, 1H), 7.39 (t, J = 111Hz) , 1H), 8.05 (s, 1H), 8.48 (s, 1H)

(Example 2 1 2) 7-(3-Aminoazetidin 1-1-1)-1-(3-Amino 1, 4-6-Gifnore-Orofenini-1)-6-Kuro-1 8 — phenol 1, 4 — dihydro 4 1 oxoquinoline 13 3 carboxylic acid:

 1 1 (3 — Amino 1, 4, 6 — Gifnoreo Lofeninore) 1 6 — Krollo 7, 8 — Gifuru 1 1, 4 ーThe title compound was obtained in the same manner as in Example 60 except that oxoquinoline-13-potassolevonic acid and 3-amino azetidin dihydrochloride were used.

Properties: light yellow powder

 i insect point: 190-193 ° C

¹ HNMR (d ₆ — DMSO) δ;

 3.65-3.77 (m, 1H), 3.97-4.10 (m, 2H), 4.52-4.68 (m, 2H), 5. 4 4 (brs, 2H), 7.07 (t, J = 8Hz, 1H), 7.38 (t, J = 11Hz, 1H), 7.96 (s , 1 H), 8.45 (s, 1 H)

 (Example 2 13)

Ethyl 8 — Chlorine 11 (41 Chlorine 2 — Phoreo Mouth 1 5 — Nitroh Mouth Mouth) 1 6, 7 — Diphnoroleur 1, 4 Draw 1 4 — Osokino Lin 3 — Power Output Box: Ethno 8 8 — Black 1 — (4 1 Black 1 2 — Black 1 2 2 6) 7-Diphnoleo 1-1, 4-Dihydro 1-4-oxoquinoline 3-Forced use of the box The title compound was obtained in the same manner as in Example 97. Properties: colorless powder

Melting point: 206-208 ° C

¹ HNMR (CDC 1 a) δ;

 1.40 (t, J = 7 7, 3Η), 4.40 (q, J = 7Η, 2Η), 7.57 (d, J = 9Η,

1Η), 8.16 (d, J = 7Η, 1Η), 8.30 (s, 1Η), 8.34 (t, J = 10 0, 1 1)

 (Example 2 14)

 No. 8 — Chromo 1 — (4 1 cro 1 6 — Fnoreo 1 — 3 — Honore 1, 6 — 7 ジ 1, 4—Jihdro 4—Okisokinorin 3—Power output box:

 Ethyl 8 — Chromo 1 — (4 1 cro 1 2 — Fluoro — 5 — 2 Tro 2) 6, 7 — Dif 1, 4 — Ji The title compound was obtained in the same manner as in Example 1666, except that dro-4-oxoquinoline-3—carboxylate was used. Properties: light brown powder

Melting point: 2 4 1 _ 2 4 4 ° C

 (Example 2 15)

 1 1 (3-Amino 4-Black 1-6-Phenolelophenyl) 1 8-Black 1-6, 7-Diffusion 1-4 4 — Oxoquinoline 1 3 — Power oleic acid:

Technology 8-Chromo 11 (41 Chromo 6-Phoreo Mouth 3-Honoré Minore Aminofenil) 1, 6-7 1,4-Dihydro 4-—oxoquinoline-3—force The title compound was obtained in the same manner as in Example 19, except for using carboxylic acid.

 Properties: light yellow powder

 Melting point: 255-258 ° C

¹ HNMR (d ₆ -DMS 0) δ;

 7.08 (d, J = 7Hz, 1H), 7.55 (d, J = 10Hz, 1H) .8.40 (t, J = 9Hz, 1H) ), 8.70 (s, 1 H)

 (Example 2 16)

 7 — (3 — Aminoa zetidin 1 1 — Innore) 1 1 — (3 — Amino 1 4 — Black mouth 6 — Funolero Fenininore 1 8 — Black Mouth 6 — Phenole Mouth 1, 4-Dihydro 4- 4-oxoquinoline 13 — Carbonic acid:

 1 1 (3-Amino 1-4-Kuro 1 6)-8-Kuro 1 6, 7-Gif 1, 1-4-Ji 1 4—oxoquinoline 3—potassium oleic acid and 3-amino azetidin dihydrochloride were obtained in the same manner as in Example 60 except that the title compound was obtained. .

Properties: light yellow powder

Melting point:> 290 ° C

¹ HNMR (d ₆ — DMSO) δ;

3.6 6-3.79 (m, 1st), 4.00-4.15 (m, 2nd), 4.60-4.74 (τη, 2nd), 5. 6 1 (brs, 2 Η), 7.00 (d, J = 10 Η ζ, 1 H), 7.50 (d, J = 10 Hz, 1 H), 7.87 (d, J = 14 Hz, 1 H)

 (Example 2 17)

 No. 1 1 (3 — t — Butoxynone Poninole Amino 4 — Fnorlaur 2 — Methox Fyno 2) 1, 6 — 7 — Gifnoreo 1 , 4 ロ 4 4 — — — — — — — — — — — — — —

 Technology 3 — Chlores 2, 4, and 5 — Trifluorobenzol acetate, 3-t — Butanol The title compound was obtained in the same manner as in Example 102 except for using Fluoro-2-Methoxyanilin.

Properties: light yellow powder

Melting point: 1 84-1 89 ° C

 'H NMR (CDC1a) δ;

 1.39 (t, J = 7 Hz, 3 H), 3.64 (s,

3H), 4.39 (q, J = 7Hz, 2H), 6.05 (brs, 1H), 7.06 (t, J = 8Hz, 1H), 7 .2 1-7.29 (m, 1H), 8.31-8.40 (m, 2H)

 (Example 218)

 1 — (3 — Amino 4 — Phono Leo 2 — Methoxy Chlorine) 1, 6, 7 — Di Phono Leo 1, 1, 4-Dihydro 4-oxo Quinoline 1 3—force oleic acid:

No. 1 — (3 — t — Butokishonore Poni Nomina 1 4 — Funoleo 2 — Methoxyfenyl) 1, 6 — 7 Mouth 1, 4 — Dihydro 41-oxoquinoline 3 _ Canoleboxylate The title compound was obtained in the same manner as in Example 103 except that canolepoxylate was used. Was.

Properties: light yellow powder

Melting point: 203-215 ° C (decomposition)

1 HNMR (d ₆ — DMSO) δ;

 6.43 (s, 3 Η) .6.78 — 6.90 (m, 1H), 7.08 (t, J = 8 Η Η, 1 Η), 8 · 4 2 (t , J = 7 Η ζ, 1), 8.61 (s, 1 Η) [Example 2 19]

 7 — (3 — Aminoa zetidin-1-1) (1-3-Amino-1-4-Fnoreo-1-2-Methoxy fever) 1-6-F Luro 1, 4 — Dihydro 1 4 — Oxoquinoline 1 3 — Power

 1 — (3 — Amino 1 4 — Fluorine 2) 1, 6 — 7 — 1, 4 — Dihydro 1 4 — O 1 Example 11 Using quinoline 3 — carboxylic acid, 3 — aminoazetidin dihydrochloride, and Ν — methylpyrrolidin. The title compound was obtained in the same manner as described above.

Properties: colorless powder

Melting point:〉 179 ° C (decomposition)

¹ HNMR (d ₆ -DMS 0) δ;

3.42 (s, 3H), 3.96-4.13 (m, 2 words), 4.55-4.72 (m, 2 words), 5.40 (brs, 3H) 2 Η), 6.7 1-6.8 3 (m, 1 Η), 7.03 (t, = 7Hz, 1H), 7.88 (d, J = 14Hz, H), 8.39 (s, 1H) [Example 220]

 Technology 6, 7, 8 — Tricro mouth 1 — (3 — Benzirokisika-Ruboni-Lua-Mino- 1, 4, 6 — Gifnore-Oro-Feni-Norre) — 1, 4 — 1 4 4 — — — — — — 3 3 力 3 3 ：

 2,3,4,5—Tetraclo vent benzoin oleate acetate and 3—Benzozoreokishonorenpo 2,2—4—Difluoro The title compound was obtained in the same manner as in Example 102 except that r-m-phenylenediamine was used.

Properties: light yellow powder

Melting point: 1 2 8 — 1 2 9 ° C

_{^{1 HNMR (CDC 1 3) δ}} ;

 1.40 (t, J = 7Η, 3Η), 4.40 (q, J = 7Η, 2Η), 7.03-7.14 (m, 2Η),

7.40 (s, 5 Η) 8 2 7 (s, 1 Η), 860 (s, 1 Η)

 (Example 22 1)

 1 1 (3—Amino 4, 6—Diphenylophenyl) 1 6,7,8-Trichloro 14 4—Dihydro 4—Oxokinori 1-3 — carboxylic acid:

Technology 6, 7, 8 — Trichlore 11 (3 — Benzirokishka Norreboni Nomino 1-4, 6 — Gifnore Olofeninore) — 1 , 4 ヒ 一 4 4 — 4 — — 3 3 — 3 力 The title compound was obtained in the same manner as in Example 103 except that a Shield was used.

Properties: colorless powder

Melting point: 25 1-25 2

_{^{1 HNMR (d 6 - DMSO)}} δ;

 7.01 (t, J = 8Hz, 1H), 7.41 (t, J = 10Hz, 1H), 8.52 (s, 1H), 8.66 (s, 1 H)

 (Example 2 2 2)

 Ethyl 11 (3—Amino 1 4 6—Diphenylolenyl) 1 6,7—Diphenylol 8—Methyl 1 4 1 Dihydro 4 1 3-Carboxylate:

 The title compound was obtained in the same manner as in Example 201, except that ethenol 2,4,5—trifluor 3—methyl benzoyl acetate was used.

Properties: light yellow powder

Melting point: 2 2 1-2 2 3. C

¹ HNMR (CDC 13) δ;

 1.38 (t, J = 7Hz, 3H), 1.85 (s, 3H), 3.98 (brs, 2H), 4.37 (q, J = 7H z, 2H), 6.8 1 (t, J = 8Hz, 1H), 7.02 (t, J = 10Hz, 1H), 8.

1 9 (t, J = 10 Hz, 1 H) 8.3 2 (s, 1 H)

(Example 2 2 3) 1-(3-amino 4, 6-diphenyl phenyl) 1-6, 7-diphenyl-8-methyl 1-1, 4-dihydro 4-1 year old Soquinoline 1 3 — Force oleic acid:

 Echinole 1 — (3—Amino 4 and 6—Diphenylolenophenol) 1 6 and 7—Difluoro 8—Methyl 1 and 4—Dihydro 4 The title compound was obtained in the same manner as in Example 103 except that oxoquinoline-3—carboxylate was used.

Properties: light yellow powder

Melting point: 2 6 4 — 2 6 7 ° C

_{'HNMR (d 6 - DMSO)} δ;

 1.86 (d, J = 3 3 Η, 1Η), 7.12 (t, J = 8Η ζ, 1Η), 7, 4 7 (t, J = 1 1 (,, 1Η ), 8.25 (t, J = 9 Hz, 1 Η), 8.69 (s, 1 Η)

 (Example 2 2 4)

 1 — (3 — Amino 1, 4, 6 — Diphenylenelophenyl) 1 7 1 (3 — Aminomethyl 1 3 — Hydroxazetidine 1 1 1 1) 8-Krollo 6-Fully low 1, 4-Hydrology 4-Oxoquinoline 1 3-Power acid:

1 1 (3-Amino 1, 4, 6-Diphnolelophenyl) 1 8 1 Chloro 6, 7-Diphnole 1, 4-Dihidero 1 4 1 Oxoquinoline 3-Power oleic acid and 3-Aminomethinole 3-Hydroxyzazetidine dihydrochloride and Triethylamine Except for using it, the title compound was obtained in the same manner as in Example 117. Properties: pale yellow powder Melting point:〉 209 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

 2.83 (brs, 2H), 4.21 (brs, 2H), 4.52 (brs, 2H), 5.42 (brs, 2H), 6.90-0-7 10 (m, 1 H), 7.36 (t,

1H), 7.85 (d, J = 14.5Hz, 1H), 8.39 (s, 1H)

 (Example 2 2 5)

 1 — (3 — Amino 1, 4, 6 — Diphenylene phenyl) _ 7-(3 — Aminomethyl azetidin 1 1 — Isole) 1 8 — — B 1-Fluoro 1, 4-Fluorine 4-Oxoxoquinoline 3-Carbonic acid:

 1 — (3 — Amino I 4, 6 — Ji No Noreo Lo Fenni Nore) _ 8 — Kuro Ichi 6, 7 — Ji No Noroi Lo 1, 4 — Ji Hidro 1 — Example 11 was similar to Example 11 except that oxoquinoline 3—force oleonic acid and 3—aminomethyl azetidine dihydrochloride and triethylamine were used. The title compound was obtained in the same manner.

Properties: light yellow powder

Melting point:〉 2 17 ° C (decomposition)

_{1 HNMR (d 6 - DMSO +} d - TFA) δ;

2.89 (brs, 1H), 3.11 (brs, 2Η), 4.29 (brs, 2Η), 4.58 (brs, 2Η), 6.90-7 0 5 (m, 1 Η), 7.36 (t, 1 Η), 7.90 (d, J = 13 Η, 1 Η), 8.46 (s, 1 Η) (Example 2 2 6)

 1 — (3 — Amino 4, 6 — Gifnoreo lofeninole) 1 8 1 Chlorol 7 — (3 — Dimethylaminoazetidine 1 1 Nore) 1-6 — Fluorine 1,4-dihydro 1 4 1-oxoquinoline 1 3 — Power

 1 — (3 — Amino 1, 4, 6 — difluorophenyl) 1 8 1 Chlorine 6, 7 — Gifnoreolor 1, 4-Dihydro 4 1 The use of 3-carboxylate and 3-dimethylamino-azetidin dihydrochloride and triethylamine was the same as that of quinoquinolin-1-carboxylic acid. The title compound was obtained in the same manner as in Example 117.

Properties: yellow powder

Melting point:〉 25 6 ° C (decomposition)

¹ HNMR (d ₆ — DMSO) δ;

 2.07 (s, 6Η), 3.03 (brs, 1H),

4.23 (brs, 2H), 4.54 (brs, 2H),

5.41 (brs, 2H), 6.98 (t, J = 8Hz, 1H), 7.37 (t, J = 11Hz, 1H), 7.87 (d, J = 13 Hz, 1 H), 8.45 (s, 1 H)

 (Example 2 2 7)

 1 1 (3-Amino 1, 4-6-diphenyl phenyl) 1 7-(3-Aminomethyl pyrrolidine 1-1) 1-8-Cro Row 6 — Fzoreolo 1, 4-Hydroxy 4-Oxoquinoline 3-Forced oleic acid:

1 — (3 — Amino 4, 6 — Gif Noreo Lofeny Nor) 1 8 — Chlores 6 and 7 — Diphenol 1 and 4 — Dihydro 4 — Oxoquinoline 3 — Power oleic acid and 3 — Aminomethylpi The title compound was obtained in the same manner as in Example 117 except that rolidine dihydrochloride and triethylamine were used.

Properties: yellow powder

Melting point: 183.0-185.5 ° C

'HNMR (d ₆ -DMS 0) <5;

 1.50-1.80 (br, 1H), 1.85-2.10 (br, 1H), 2.35-2.60 (m, 1H), 2. 8 0 (brs, 2 H), 3.00 — 3.65 (m,

4 H), 5.45 (brs, 2 H), 6.90-7.

0 5 (m, 1 H), 7.35 (t, 1 H), 7.96 d (d, J = 12 Hz, 1 H), 8.55 (s, 1 H)

(Example 2 2 8)

 1-(3-Amino 4, 6-Diphnoreolofenenore) 1 8-Black mouth 7-(3-Hydroxycarbonylazetidine 1 1 — 1 — 4 — dihydro 1 — 4 — dihydro 4 — oxoquinoline 1 — 3 — carboxylic acid:

 1 — (3 — Amino 1, 4, 6 — Diph Norelo Fennino) 1 8 1 Black 1, 6, 7 — Diph Norelo 1, 4 — Dihydro 4 — Example 13 The same procedure as in Example 11 was carried out, except that oxoquinoline 13 -force oleonic acid and azetidin 13 -carboxylate and triethylamine were used. To give the title compound.

Properties: pale yellow powder

Melting point: 27.0-23.1 ° C ¹ HNMR (d ₆ -DMS 0) <5;

 3.25-3.60 (m, 1H), 4.50 (brs, 2H), 4.66 (brs, 2H), 5.42 (brs, 2H), 6 -9 6 (t, J = 8 Hz, 1 H), 7.37 (t, J = 10 Hz, 1 H), 7.89 (d,

J = 13.7 Hz, 1H), 8.46 (s, 1H) (Example 22 9)

 7 — (3—Amino Aminazetidine 1 1-in-no-re) 1 1-(3—Amino 1--4, 6—diphenyl phenyl) 1 6-f Norero 1, 4 -Hydroxy 4 1 -oxo 1, 8 -Naphthyridine 1-3 -Capronic acid:

 1 1 (3—Amino 1-4, 6—Diphenylophenyl) 1 7 1 Chloro 6—Phnoreo 1—1, 4-Dihydro 4—Oxo— 1,8-Naphthyridine-1 3-force olevonic acid and 3-acetylaminoazetidine hydrochloride and triethylamine The title compound was obtained in the same manner as in Example 117.

Properties: light brown powder

Melting point: 289.0-295.0

_{1 HNMR (d 6 - DMSO)} δ;

 1.81 (s, 3 layers), 3.60-490 (m,

5 Η), 5.35 (brs, 2H), 694 (t, 1H), 7.35 (t, J = 10 Η 1, 1 Η), 8.

0 6 (d, J = 10 Η 1, 1 Η), 8.54 (b rs, 1)), 8.69 (s, 1 Η)

(Example 230) 1-(3-amino 1, 4, 6-diphnolelofenyinore) 1-7 ((1R, 4R)-2, 5-diazabicyclo [2 · 2. 1] Heptane 1 2 — Innole) 1 6 — Phenorero 1, 4 — Dihydro 1 4 — Oxo 1, 8 — Naphthyridine 1 3 — Power Acid:

 1 — (3 — Amino 1, 4, 6 — diphenylene phenyl) 1 7 — Black mouth 6 — Fluorine 1, 4-dihydro 1 -4 oxo — 1, 8 — naphthyridine 13-carboxylate and (1R, 4R) 12, 5-diazabicyclo [2.2.1. 1] heptane dihydrochloride The title compound was obtained in the same manner as in Example 117 except that triethylamine was used.

Properties: pale yellow powder

Melting point:〉 2 84 ° C (decomposition)

'HNMR (d ₆ — DMSO + d-TFA) δ;

 1.90 (d, J = l l H z, 1 H), 2.11 (d,

J = 11 Hz, 1 H), 3.15-3.90 (m, 5H), 4.45 (s, 1H), 5.20-6.10 (br, 2H), 6.98 (t, 1H), 7.36 (t, J = 10Hz, 1H), 8.18 (d, J = 12Hz, 1H) , 8.76 (s, 1 H), 9.15-9.30 (br, 2 H)

 (Example 23)

1 — (3 — Amino 4, 6 — Gifnoreo Lofeninore) 1 8 1 Kuro mouth 1 7 — (3, 7 — Giza bicyclo [3. 3. 0] Octane 1 3 — yl) 1 6 — Fluoro 1, 4 — Dihydro One 4 — oxoquinoline one 3 — carboxylic acid hydrochloride:

 1-(4-Amino 1-4, 6-Gifnore Orofeninore) 1 8-Kuroguchi 6, 7-Gifnore 1-1, 4-Jihidoro 4 1-oxoquinoline 13-force oleonic acid lOOmg and 3-t-butoxycarbonyl 1,3,7-diazabicyclo [3.3.0] octane 10 4 mg of triethynoleamine 15 O mg was dissolved in 3 ml of sodium acetate and stirred at 80 ° C for 3 hours. The solvent was distilled off under reduced pressure. It was extracted with 30 ml of black mouth Holm. The organic layer was washed with 20 ml of a 3% aqueous solution of citric acid. It was distilled off after drying. This was dissolved in dichloromethane 2 Oml. 5 ml of 4N nodoxane hydrochloride was added, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. The residue was solidified with isopropyl ether and collected by filtration. 120 mg of the title compound was obtained as a pale yellow powder.

Properties: pale yellow powder

Melting point: 199.5-204.0 ° C

_{1 HNMR (d 6 - DMSO)} δ;

 2.85-3.10 (m, 4H), 3.30-3.70 (m, 6Η), 7.02 (t, J = 8Η, 1Η), 7 4 1 (t, J = 10 Hz, 1Η), 8.08 (d,

J = 12.5 Hz, 1 H), 8.59 (s, 1H), 9.13 (brs, 1H), 9.26 (brs, 1H) [Example 23 2]

1 — (3 — Amino 1, 4, 6 — Gifnoole orophenyl) 1 7-(3, 7 — Jazabicyclo [3.3.0] octane 1 Three -6-phenolic mouth-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-phenolic acid hydrochloride:

 1 — (3 — Amino 4, 6 — diphenyl phenyl) 1 7 1 Chlor 6 — Pheno 1, 4-dihydro 4 1 oxo 1 1, 8 — Naphthyridine 1 3 — Potassium benzoate and 3 — t — Butoxycanolebonyl 1, 3, 7 — Diazabicyclo [3. 3. 0] The title compound was obtained in the same manner as in Example 231, except that octane was used.

Properties: pale yellow powder

Melting point: 203.0-208.0 ° C

_{'HNMR (d 6 - DMSO)} δ;

 3.06 (brs, 4H), 3.36 (brs, 2H), 3.40-3.90 (m, 4H), 7.12 (t, 1H), 7 4 2 (t, J = 1 1z, 1 H), 8.09 (d, J = 13 Hz, 1 H), 8.72 (s,

1 H), 9.46 (brs, 2 H)

 (Example 23)

 1 — (3 — Amino 4, 6 — Gifnorelophenyl) 1 7 1 (3, 7 — Gizabicyclo [3.3.0] Octane 1 3 — Inole) 1 6 — Phenole 1-1, 4 — Dihydro 1-41-oxoquinoline-3 — Carboxylic acid hydrochloride:

1 — (3 — Amino 1, 4, 6 — difluoro phenyl) 1, 6, 7 — difluoro 1, 4 — dihydro 1 4 1 oxoquinoline Other than using octane, 3-force olevonic acid and 3-t-butoxynole pononiole 3, 7-diazabicyclo [3.3.0] The title compound was obtained in the same manner as in Example 23.

 Properties: yellow powder

 Melting point: 2 2 1-2 24.5 ° C

1 HNMR (d ₆ -DMS 0) δ;

 2.95-3.20 (m, 4Η), 3.25-3.65 (m, 6Η), 6.06 (d, 1Η), 7.12 (t, 1Η), 7.53 (t, 1Η), 7.91 (d, J = 14 4, 1Η), 8.67 (s, 1Η), 9.30-9 . 7 0 (br, two words)

 (Example 2 3 4)

 1 1 (3—Amino 4 and 6—Difluorophenyl) 1 7 1 (3—Amino ethyl azetidin 1 1-yl) 1 8—Cro Ro 6 — phenol 1, 4-dihydro 1 4 — oxoquinoline 3 — carboxylate trifluoroacetate:

 1 1 (3—Amino 4 and 6—Diphenylophenyl) 18 1 Chromo 6 and 7—Diful 1 and 4—Dihydro 1 4 1 For oxoquinoline 3-force oleic acid and 3-t-butoxy carbonyl diamine azetidin and triethylamine The reaction was carried out in the same manner as in Example 231, except for the above. For deprotection, the title compound was obtained using trifluoroacetic acid instead of 4N hydrochloride-dioxane.

Properties: yellow powder

Melting point: 140.0-141.5 ° C

_{1 HNMR (d 6 - DMSO)} δ;

1.80-1.95 (m, 2H), 2.60 — 2. 8 5 (m, 3 H), 4.14 (brs, 2 H), 4.57 (brs, 2 H), 6.95 (dd, J = 7 Hz, J = 9 Hz, 1 H), 7.36 (t, J = 11 Hz, 1H), 7.70 (brs, 3H), 7.87 (d, J = 13.5 Hz, l H), 8.45 (s, l H)

(Example 2 3 5)

 5—Penzinole Oxy 1 1 — (3—Penzinole Okishonore Boninore Amino 1, 4 — 6—Diphnole Lofin 2) 1 6, 7, 8 Trinole mouth 1, 4 — Dihydro 4 — Oxoquinoline 1 3 — Power

Echinole 6-benzyloxy 2,3,4,5 -tetranoreole benzoinoleate acetate 1.1 g, orthochinate 0.75 ml and acetic anhydride 0.85 ml were stirred at 130 ° C for 1 hour. Distilled off under reduced pressure. To the residue was added 10 ml of dichloromethane. To this was added 0.8 g of N-benzyloxycanolevonil-1,2,4-diphenol-1 m-phenylenediamine, and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. This was dissolved in 3 ml of N, N-dimethinolehonolem amide. 0.41 g of potassium carbonate was added, and the mixture was stirred at 100 ° C for 10 minutes. 50 ml of 5% citric acid was added to the reaction solution. The mixture was extracted with 50 ml of a closed mouth form. The organic layer was washed with a saturated saline solution and dried with magnesium sulfate. Distilled off under reduced pressure. The residue was applied to a column chromatograph (silica gel, chlorophenol Z acid etch = 20 Z1). The above compound of red oil 1. 4 g ₀ obtained Properties: red oil

¹ HNMR (CDC 13) δ;

 1.37 (t, J = 7 Hz, 3 H), 4.38 (t, J = 7 Η, 2 Η), 5.2 1 (s, 1 Η), 5.

26 (s, 1 Η), 70 1 (s, 1 Η), 7.08 (t, J = 10 Η, 1 Η), 7.2 5-7.55 5 (brs, 8 Η), 7.55-7.65 (m, 2 Η), 8.14 (s, 1 Η) 8.40 (brs, 1 Η) [Example 23 6]

 1 1 (3—Amino 4, 6-diphenyl phenol) 1 5-Hydroxy 1 6, 7, 8 — Tri-norep 1-, 4-Dihydro B 4 1-oxo quinoline 3 — Power oleic acid:

 1.3 g of the compound synthesized in Example 23 was added to 8 ml of acetic acid, 10 ml of 6N-hydrochloric acid, and the mixture was stirred at 100 ° C for 4 hours. The solvent was distilled off under reduced pressure. Water was added to the residue. The solid was collected by filtration. Washed with water, ethanol and isopropyl ether. 0.55 g of the above compound was obtained as a yellow solid.

Properties: yellow powder

Melting point:〉 278.0 ° C (decomposition)

_{1 HNMR (d 6 - DMSO)} δ;

 5.47 (brs, 2H), 7.08 (dd, J = 8Hz, J = 9Hz, 1H), 7.41 (dd, J = 10Hz, J = 1 1 H z, 1 H), 8.5 9 (s, 1 H)

(Example 23) 1 1 (3—Amino 4 and 6—Diphenylene) 1 7- (3—Aminoa zetidin-1 1-inole) 16 and 8—Difur Orro 5 — Hydroxy 1, 4-Hydroxy 4 — Oxoquinoline 1 3 — Carbonic acid:

 1 1 (3—Amino 1,4,6—Diphenylophenyl) 1 5—Hydro 1-6,7,8—Trifluoro1 1,4—Jihid Example 4 Example 7 was the same as Example 11 except that 3-oxoquinoline-3—force oleonic acid and 3—aminoazetidin dihydrochloride and triethylamine were used. The title compound was obtained in the same manner.

Properties: yellow powder

Melting point:〉 26 1 ° C (decomposition)

¹ HNMR (de-DMSO + d-TFA) δ;

 3.93 (b rs, 1 H), 4.14 (b rs, 2 H),

4.48 (brs, 2H), 5.43 (brs, 2H), 7.04 (t, 1H), 7.36 (t, J = 10Hz,

1 H), 8.36 (s, 1 H)

 [Test Example 1]

Antibacterial action:

The minimum inhibitory concentration (MIC: g / \) was measured according to the standard method of the Japanese Society of Chemotherapy (CHEMOTHERAPY, 29 (1), 76.1981). Table 1 shows the results. ¾ 1

(Test Example 2)

Cytotoxicity test:

96% pellet of 10% fetal bovine serum, 0.1 mM non-essential amino acid-added Eagle MEM suspended in Eagle MEM medium was added to each plate of the tissue culture plate. Three cells and IMR32 cells (each 5 × 10 ³ cells, 4 × 10 ⁴ cells) were inoculated. Added various concentrations of drug, 3 7 6 hours at 5% C 0 ₂ presence, fixed in 5% glutarate Ruarude arsenide de After completion of the culture, and stained with 0.0 5% main switch les Nburu. Further, the dye was extracted with 0.3 NHC 1, and the absorbance was measured at a wavelength of 65 nm to obtain an IC ₅ . The value was calculated. Table 2 shows the results. Table 2

 [Test Example 3]

 Phototoxicity test:

The test compound was administered intravenously (40 mg / kg, 10 ml) to female ICR mice (5-6 weeks of age) and then exposed to ultraviolet light (320-400 nm, 1.8 mWZ cm). ² Z sec) for 4 hours. The time immediately after the irradiation was set to 0 hours, and abnormalities in the ears were observed 24 and 48 hours later. Ear abnormalities were rated as no abnormalities (0 points), mild erythema (1 point), moderate erythema (2 points), severe erythema or edema (3 points). Table 3 shows the results.

 Table 3

 [Test Example 4]

Chromosome aberration test:

Eagle MEM with 10% fetal bovine serum in 60 mm schale They were inoculated with CHL cells suspended in the medium (0. 2 ~ 2 xl 0 5 pieces Nou Weru). The cells were pre-cultured for 3 to 4 to 72 hours in the presence of 5% (: 0 ₂ 37), replaced with a medium containing various concentrations of the drug, and then cultured under the same conditions. In the case of the S9 supplemented medium, the medium was cultured for 6 hours, and then replaced with the drug and S9-free medium for an additional 18 hours.In the case of the direct method, 24 hours and 48 hours were used. After culturing, a chromosome sample was prepared based on the standard method of the Japanese Society for Environmental Mutagen Research, and 100 metaphase images were observed by microscopy. Calculated percentage o

 As a result, the compounds of Example 48 and Example 117 were negative from 0 to 200 βg / m 1.

Claims

The scope of the claims

1. The following general formula (1)

[In the formula, R ′ represents a hydrogen atom or a carboxyl protecting group, R ² represents a nitro group or a substituted or unsubstituted amino group, and R ³ represents a halogen atom. R ⁴ and R ⁵ represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group which may be the same or different, and R ⁶ represents a hydrogen atom, a halogen atom. , A hydroxy group, a lower alkyl group or an amino group, R ⁷ represents a hydrogen atom or a halogen atom, A represents a nitrogen atom or —CX = (where X represents a hydrogen atom, Represents a halogen atom, a lower alkyl group or a lower alkoxy group), and Z represents a halogen atom or a saturated cyclic amino group which may have a substituent. ] The pyridone carboxylic acid derivative represented by these, or its salt.

 2. An antibacterial agent comprising the pyridone carboxylic acid derivative or a salt thereof according to claim 1 as an active ingredient.