KR950018000A - Novel quinolone derivatives and preparation methods thereof - Google Patents

Abstract

The present invention relates to a quinolone derivative represented by the following general formula (I) and a pharmaceutically acceptable acid addition salt thereof.

Wherein R ₁ is a chain or cyclic lower alkyl group having 1-3 carbon atoms, a halogen or substituted chain or cyclic lower alkyl group having 1-3 carbon atoms, a phenyl group or 1-2 halogen substituted Phenyl group; R ₂ is a hydrogen atom, a lower alkyl group or an amino group; R ₃ is a halogen atom or a heterocyclic compound containing at least one nitrogen atom in a ring with a substituted or unsubstituted hetero atom, represented by the following general formula (A),

Wherein R ₆ , R ₇ , R ₈ and R ₉ are each hydrogen atoms or lower alkyl groups, two of which may form a bond with each other, m and n are from 0 to 1 and Ca-Cb forms a bond Or a single bond or a double bond); X represents a nitrogen atom or CR ₄ , wherein R ₄ represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; Y and Z are either halogen or trifluoromethyl and the other is hydrogen or halogen, such as ester group, cyano group, nitro group, fluorine, trifluoromethyl, substituted or unsubstituted amide group, lower alkyl slot width Electron attracting groups, such as a cyclic or lower alkylsulfonyl group, are shown.

The present invention also relates to an antimicrobial agent containing the compound of formula (I) as an active ingredient.

Description

Novel quinolone derivatives and preparation methods thereof

Since this is an open matter, no full text was included.

Claims (11)

The novel quinolone derivatives represented by the following general formula (I) and pharmaceutically acceptable acid addition salts thereof. Wherein R ₁ is a chain or cyclic lower alkyl group having 1-3 carbon atoms, a halogen or substituted chain or cyclic lower alkyl group having 1-3 carbon atoms, a phenyl group or 1-2 halogen substituted Phenyl group; R ₂ is a hydrogen atom, a lower alkyl group or an amino group; R ₃ is a halogen atom or a heterocyclic compound containing at least one nitrogen atom in a ring with a substituted or unsubstituted hetero atom, represented by the following general formula (A), Wherein R ₆ , R ₇ , R ₈ and R ₉ are each hydrogen atoms or lower alkyl groups, two of which may form a bond with each other, m and n are from 0 to 1 and Ca-Cb forms a bond Or a single bond or a double bond); X represents a nitrogen atom or CR ₄ , wherein R ₄ represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; Y and Z are either halogen or trifluoromethyl and the other is hydrogen or halogen, such as ester group, cyano group, nitro group, fluorine, trifluoromethyl, substituted or unsubstituted acyl group, substituted or substituted Electron attracting groups, such as an amide group, a lower alkyl sulfoxy group, or a lower alkyl sulfonyl group, which are not represented. The compound of claim 1, wherein R ₁ is a cyclopropyl group and R ₃ is a substituted or unsubstituted 3-methylaminopyrrolidine group. The compound according to claim 1 or 2, wherein the compound of formula (I) is one of the following compounds or an acid addition salt thereof; 1-cyclopropyl-6-fluoro-8-methoxy-7- (3-methylaminopyrrolidin-1-yl) -3- (2-fluoro-2-methoxycarbonyl) acetyl-4- Oxo-1, 4-dihydroquinoline hydrochloride; 1-cyclopropyl-6-fluoro-8-methoxy-7- (3-methylaminopyrrolidin-1-yl) -3- (2-fluoro-2-acetyl) acetyl-4-oxo-1 4-dihydroquinoline hydrochloride; 1-cyclopropyl-6-fluoro-8-methoxy-7- (3-methylaminopyrrolidin-1-yl) -3- (2-fluoro-2-fluoroacetyl) acetyl-4-oxo 1, 4-dihydroquinoline hydrochloride; 1-cyclopropyl-6-fluoro-8-methoxy-7- (3-methylaminopyrrolidin-1-yl) -3- (2-fluoro-2-difluoroacetyl) acetyl-4- Oxo-1, 4-dihydroquinoline hydrochloride; Or 1-cyclopropyl-6-fluoro-8-methoxy-7- (3-methylaminopyrrolidin-1-yl) -3- (2-fluoro-2-trifluoroacetyl) acetyl-4 Oxo-1,4-oxoquinoline hydrochloride. An antimicrobial agent comprising the compound of claim 1 as an active ingredient. (a) activating a compound of formula (II) using a carboxylic acid active reagent to produce a compound of formula (III); (b) reacting a compound of formula (III) with a compound represented by M ^{n +} Y—CH—Z to prepare a compound of formula (IV); And (c) deprotecting the compound of general formula (IV) to produce a compound of general formula (I). In the above schemes, Act, Act ₁ and M ^{n +} represent a carboxylic acid active reagent, an activated carboxyl group, an alkali or alkyl earth metal ion, etc., respectively, and R ₁ , R ₂ , R ₃ , X, Y and Z Is as defined in claim 1, and R ₁₅ is R ₃ in an amine group protected state. (a) reacting a compound of formula (V) with an acyl halide or organic acid anhydride to produce a compound of formula (VI); And (b) deprotecting the compound of general formula (VI) to produce a compound of general formula (I). In the above scheme, R ₁ , R ₂ , R ₃ , R ₁₅ , X, Y and Z are as defined in claim 1. (a) activating a compound of formula (II) using a carboxylic acid active reagent to produce a compound of formula (III); (b) converting a compound of formula (III) to Reacting with a compound to produce a compound of formula (VII); And (c) deprotecting the compound of general formula (iii) to produce the compound of general formula (I). In the above scheme, R ₁ , R ₂ , R ₃ , R ₁₅ , X, Z, Act and Act ₁ are as defined in claim 1. 8. The reaction temperature of claim 5, wherein the deprotection reaction is performed at a reaction temperature of 0 ° C. to 80 ° C. under 1-10% HCl-methanol solution and CF ₃ CO ₂ H or 1-10% HCl-ethyl acetate solution. How is done in. 8. A solid according to claim 5 or 7, wherein the salt of the compound of formula (I) is dissolved in water to adjust the pH to about 7. Dissolving in water and adding a pharmaceutically acceptable organic or inorganic acid. 10. The process of claim 9, wherein the lower alcohol is ethanol or methanol and the haloalkanes are chloroform, dichloromethane or 1, 2-dichloroethane. The organic acid of claim 9, wherein the organic acid is selected from the group consisting of lactic acid, ascorbic acid, maleic acid, malonic acid, glutamic acid, citric acid, fumaric acid, paratoluene sulfonic acid, acetic acid, trifluoro acetic acid, propionic acid, tartaric acid, succinic acid, methanesulfonic acid, and the like. The selected acid, and the inorganic acid is selected from the group consisting of hydrochloric acid, sulfuric acid or nitric acid. ※ Note: The disclosure is based on the initial application.