SI8911674B - Spiro compounds - Google Patents

Claims (7)

-118-- CLAIMS -118-- 1. Spiro compound of formula I (CH2) b- c- < ch2 \ (CH2) c h-Q z- (CH2) {I in which a represents an integer 0 or 1; b represents an integer from 2 to 5 inclusive; c represents an integer 0 or 1; and d represents an integer from 0 to 2 inclusive; Z represents > CHR1 · > NR2, > C = NOR3, an oxygen atom or a sulfur atom, wherein R1 represents a hydrogen atom, an amino group, a monoalkylamino group having 1 to 6 carbon atoms, a dialkylamino group containing 1 to 6 carbon atoms in each alkyl, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms or a hydroxyalkyl group having 1 to 6 carbon atoms; R 2 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a hydroxyalkyl group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, a formyl group or an alkylcarbonyl group having 2 to 7 carbon atoms; and R3 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; Q represents a partial structure of formula II: II in which R4 represents an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 2 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, cis-2-methylcyclopropyl, 2-gem -dihalocyclopropyl, 4-fluorophenyl, 2,4-di-fluorophenyl, 2-fluoro-4-pyridyl, an alkoxy group having 1 to 6 carbon atoms or an alkylamino group having 1 to 6 carbon atoms; R5 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms; R 6 represents a hydrogen atom, an amino group, a mono-C 1 -C 4 -alkylamino group, a di-C 1 -C 4 -alkylamino group, a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms or a halogen atom; A represents a nitrogen atom or -119- wherein R7 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a halogen atom, an alkoxy group having 1 to 6 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms or a given group; R 4 may form together with R 5 and / or R 7 a substituted or unsubstituted 4- to 7-membered ring, which may include an oxygen, nitrogen or sulfur atom in which the substituent is an alkyl group having 1 to 6 carbon atoms or a haloalkyl group having 1 to 6 carbon atoms; X represents a halogen atom; Y represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxyalkyl group having 1 to 6 carbon atoms, a phenylalkyl group containing 1 to 6 carbon atoms in its alkyl moiety, a dihabol group, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, ethoxycarbonyloxy group, choline group, dimethylaminoethyl group, 5-indanyl group, phthalidinyl group, 5-substituted-2-oxo-1,3-di-oxazol-4 * ylmethyl group or 3-acetoxy-2-oxobutyl group, and its salts . Spiro compound of formula I according to Claim 1, characterized in that a 1, b is 2, c is 0 and d is 1 and Z represents > CH (NH 2), or a salt thereof. Spiro compound of formula I according to Claim 1, characterized in that a 1, b is 3, c is 0 and d is 1 and Z represents > CH (NH 2), or a salt thereof. Spiro compound of formula I according to Claim 1, characterized in that a 1, b is 2, c is 0 and d is 2 and Z represents > NH, or a salt thereof. Spiro compound of formula I according to claim 1, characterized in that said spiro compound is selected from the group consisting of 7- (7-amino-5-azaspiro / 2,4 / heptan-5-yl) -1 -cyclopropyl-6,8-di-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 7- (7-amino-5-azaspiro / 2,4 / heptan-5-yl) -8- Chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, -120- 7- (7-amino-5-azaspiro / 2,4 / heptan-5-yl) - 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 7- (7-amino-5-azaspiro-2,4-heptan-5-yl) -6-f Chloro-1- (2,4-difluorophenyl) -1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 7- (7-amino-5-azaspiro / 2,4 / heptan-5-yl) - 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 10- (7-amino-5-azaspiro / 2,4 / heptan-5-yl) -9-fluoro-2,3-dihydro-3- (S) -methyl-7-oxo-7H-pyrido [1,2,3-de] 1,4-benzoxazine-6-carboxylic acid , 1-cyclopropyl-7- (4,7-diazaspiro / 2,5 / octan-7-yl) -6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 7- (7-amino) -5-azaspiro- / 2,4 / hept an-5-yl) -1-cyclopropyl-6-fluoro-8-methyl-1,4-dihydro-4-o-xoquinoline-3-carboxylic acid, 7- (7-hydroxy-5-azaspiro / 2,4 (heptan-5-yl) -8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 7- (7-amino-5-azaspiro / 2,4) 1-Heptan-5-yl) -1- (2-methyl-2-propyl) -6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid, 7- (7- hydroxyimino-5-azaspiro [2,4 / heptan-5-yl) -8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 1-cyclopropyl-6, 8-Difluoro-7- (8-hydroxymethyl-6-azaspiro [3,4 / octan-6-yl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 1-cyclopropyl-6,8-difluoro7 - (4 * Hydroxymethyl-2-azaspiro [4,4 / nonan-2-yl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 1-cyclopropyl-6,8-difluoro-7- (4 -hydroxymethyl-2-azaspiro [4,5 / decan-2-yl) -4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 7- (8-amino-6-azaspiro / 3,4 / octane- 6-yl) -1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro--112-nonyl-3-carboxylic acid, 10- (8-amino-6-azaspiro / 3,4 / octan-6-yl) - 9-Fluoro-2,3-dihydro-3- (S) -methyl-7-oxo-7H-pyrido [1,2,3-de] 1,4 / benzoxazine-6-carboxylic acid, 7- (4) -Amino-2-azaspiro [4,4 / nonan-2-yl) -1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-inoline-3-carboxylic acid and its salts. Spiro compound of formula I according to one of claims 1 to 5, wherein said spiro compound is optically stereoisomerically pure. Process for the preparation of spiro compounds according to Claims 1 to 6, characterized in that the cyclic amine bearing the spirocyclic ring is reacted with the following formula Z- (CH2) d wherein a, b, c, d and Z are as defined in claim 1, with a halogenated quinolone derivative of the following formula R COOY in which A, R4, R5, R6, Y and X are as defined in claim 1 and X 'represents a halogen atom. For DAIICHI PHARMACEUTICAL CO., LTD .: