4-PHENYL-5-OXO-1,4,5,6,7,8-HEXAHYDROXYQUINOLINE DERIVATIVES AS MEDICINAL AGENTS FOR TREATING STERILITY Russian patent published in 2011 - IPC C07D215/20 C07D401/12 C07D405/12 C07D409/12 C07D417/12 A61K31/4709 A61P5/24 

FIELD: chemistry.

SUBSTANCE: invention relates to 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives of formula I

or pharmaceutically acceptable salts thereof, where R¹ denotes (1-6C)alkyl; R², R³ independently denote halogen, (1-4C)alkoxy; R⁴ denotes phenyl or a 5-6-member heteroaryl, having one or two heteroatoms selected from nitrogen, oxygen or sulphur, phenyl or said heteroaryl, substituted with R⁷ and optionally substituted on the (hetero)aromatic ring with one or two substitutes selected from halogen, nitro, trifluoromethyl and (1-4C)alkyl; R⁷ denotes H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R⁸R⁹-amino, R¹⁰R¹¹-aminocarbonyl, R¹²R¹³-amino(1-4C)alkylcarbonyl-amino, R¹⁴R¹⁵-amino(1-4C)alkyl, R¹⁶-oxy, R¹⁷R¹⁸-aminocarbonyl (1-4C)alkoxy, R¹⁹-oxy(1-4C)alkyl, R¹⁹-oxycarbonyl(1-4C)alkyl, R²⁰R²¹-aminosulphonyl, R²⁰-oxysulphonyl, aminoiminomethyl, (di)(1-4C)alkylaminoiminomethyl, morpholinyliminomethyl, trifluoromethylsulphonyl; R²³-oxycarbonyl, or R²³R²⁴-aminocarbonyl; R⁸ denotes H or (1-4C)alkyl; R⁹ denotes (1-4C)alkylsulphonyl, (1-6C)alkylcarbonyl, (2-6C)alkenylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, piperazinylcarbonyl, (5-8C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl or phenylcarbonyl, furylcarbonyl, thiophenylsulphonyl, 5-member heteraryl(1-4C)alkyl, having one or two nitrogen atoms, optionally substituted on the heteroaromatic ring with one, two or three substitutes selected from hydroxy, amino, halogen, nitro, trifluoromethyl, (1-4C)alkoxy; R¹⁰ denotes H or (1-4C)alkyl; R¹¹ denotes hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl; R¹², R¹³ independently denote H, (1-6C)alkyl, (3-6C)-cycloalkyl, (1-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(1-4C)alkyl, pyrrolidinyl(1-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)-alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl, pyridinyl (1-4C)alkyl; or R¹²R¹³ in R¹²R¹³-amino(1-4C)alkylcarbonylamino can be bonded together with the nitrogen atom to which they are bonded into a (5-6C)heterocycloalkyl ring, having one or two nitrogen atoms, optionally substituted with hydroxy(1-4C)alkyl; R¹⁴, R¹⁵ independently denote H, (1-6C)alkyl, (1-6C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyridinyl(1-4C)alkyl, optionally substituted on the aromatic ring with one substitute selected from halogen; or R¹⁶ denotes (di)(1-4C)alkylamino(2-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, phenyl(1-4C)alkyl or pyridinyl(1-4C)alkyl; R¹⁷, R¹⁸ independently denote H, (1-6C)alkyl, thiophenyl(1-4C)alkyl; or R¹⁷R¹⁸ in R¹⁷R¹⁸-aminocarbonyl(1-4C)alkoxy can be bonded into a morpholine or piperazine ring, R¹⁹ denotes H or (1-6C)alkyl; R²⁰R²¹ independently denote H, (1-6C)alkyl or (1-4C)alkoxy(1-4C)alkyl; or R²⁰R²¹ in R²⁰R²¹-aminosulphonyl can be bonded into a morpholine ring; X denotes O or N-R²²; Y denotes CH₂ or C(O); Z denotes CN or NO₂; R²² denotes H; R²³, R²⁴ independently denotes H; (1-4C)alkyl; or R²³R²⁴ in R²³R²⁴-aminocarbonyl can be bonded into a dihydropyridine ring; provided that compounds of formula I, in which X denotes O, R⁴ denotes phenyl and R⁷ is selected from H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R²³-oxycarbonyl, and R²³R²⁴-aminocarbonyl, and compounds of formula I, in which X denotes O, R⁴ denotes (2-5C)heteroaryl and R⁷ denotes H are excluded. The invention also relates to use of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives to prepare a medicinal agent for treating sterility.

EFFECT: improved useful biological properties.

12 cl, 73 ex