RU2007144985A - DIGIDROPYRIDINE DERIVATIVES - Google Patents

Abstract

1. Derivative of dihydropyridine of the formula 1! ! formula I! or a pharmaceutically acceptable salt thereof, in which! R1 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or phenyl, C1-5 heteroaryl, both optionally substituted with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy groups, C1-4 (di) alkylamino groups; ! R2, R3 are independently C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy, C2-4 alkenyloxy, C3-4 alkynyloxy, halogen; ! R4 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C3-6 cycloalkyl C1-4 alkyl, C2-6 heterocycloalkyl, C2-6 heterocycloalkyl C1-4 alkyl or C6-10 aryl, C6-10 aryl C1 9 heteroaryl, C1-9 heteroaryl C1-4 alkyl, wherein the (hetero) aryl group is optionally substituted with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxy , C1-4 (di) alkylamino groups, and if R4 is phenyl, further from C1-4 alkylthio group, C1-4 alkyl sulfonyl, R5-hydroxycarbonyl, R5-carbonyl or R5, R6-aminocarbonyl; ! X is SO2, CH2, C (O) or X is absent, wherein if X is CH2, R4 may further be R5-hydroxycarbonyl, or R5-carbonyl; ! R5, R6 are independently H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkyl C1-4 alkyl, C2-6 heterocycloalkyl, C2-6 heterocycloalkyl C1-4 alkyl, C1-4 alkoxycarbonyl C1-4 alkyl, C1-4 ) alkylaminocarbonyl C1-4 alkyl or C6-10 arylaminocarbonyl C1-4 alkyl, C1-9 heteroarylaminocarbonyl C1-4 alkyl, C6-10 aryl, C1-9 heteroaryl, C6-10 aryl C1-4 alkyl,

Claims (12)

1. Derivative of dihydropyridine of the formula 1

formula I or its pharmaceutically acceptable salt, in which R ¹ is C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl or phenyl, C _1-5 heteroaryl, both optionally substituted with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano C _1-4 alkyl; C _2-4 alkenyl; C _2-4 alkynyl; C _1-4 alkoxy; C _1-4 (di) alkylamino; R ² , R ³ independently are C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _2-4 alkenyloxy, C _3-4 alkynyloxy, halogen; R ⁴ is C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _3-6 cycloalkyl C _1-4 alkyl, C _2-6 heterocycloalkyl, C _2-6 geterotsikloalkilS _1-4 alkyl or C _6-10 aryl, C _6-10 arylC _1-4 alkyl, C _1-9 heteroaryl, C _1-9 geteroarilS _1-4 alkyl, wherein the (hetero) aryl group optionally substituted by one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 (di) alkylamino , and if R ⁴ is phenyl, additionally from C _1-4 alkylthio groups, C _1-4 alkylsulfonyl, R ⁵ -oxycarbonyl, R ⁵ -carbonyl or R ⁵ , R ⁶ -aminocarbonyl; X is SO ₂ , CH ₂ , C (O) or X is absent, wherein if X is CH ₂ , R ⁴ may further be R ⁵ -oxyacarbonyl, or R ⁵ -carbonyl; R ⁵ , R ⁶ are independently H, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkyl, C _1-4 alkyl, C _2-6 heterocycloalkyl, C _2-6 geterotsikloalkilS _1-4 alkyl, C _1-4 alkoksikarbonilS _1-4 alkyl, C _1-4 (di) alkilaminokarbonilS _1-4 alkyl or C _6-10 arilaminokarbonilS _1-4 alkyl, C _1-9 geteroarilaminokarbonilS _1-4 alkyl, C _6-10 aryl, C _1-9 heteroaryl, C _6-10 aryl C _1-4 alkyl, C _1-9 heteroaryl C _1-4 alkyl, wherein the (hetero) aryl group is optionally substituted with one or more substituents selected from hydroxy , amino, halogen, nitro, trifluoro methyl, cyano, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 (di) alkylamino or R ⁵ , R ⁶ in the R ⁵ , R ⁶ -aminocarbonyl group may be bonded to the C _2-6 heterocycloalkyl ring; with the proviso that the compound is not 2-methyl-5-oxo-7-phenyl-4- (3,4,5-trimethoxyphenyl) -1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile. 2. The compound according to claim 1, in which R ⁴ is phenyl optionally substituted with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, C _1-4 alkyl, C _2-4 alkenyl, C _{2 -4} alkynyl, C _1-4 alkoxy, C _1-4 (di) alkylamino groups, C _1-4 alkylthio groups, C _1-4 alkylsulfonyl, R ⁵ -oxycarbonyl, R ⁵ -carbonyl or R ⁵ , R ⁶ -aminocarbonyl. 3. The compound according to claim 2, in which the substituent in the phenyl group in R ⁴ is R ⁵ , R ^{6 is} aminocarbonyl, C _1-4 alkoxy and / or halogen. 4. The compound according to claim 3, in which R ⁵ , R ⁶ in the R ⁵ , R ⁶ -aminocarbonyl group is a C _1-4 (di) alkylamino group. 5. The compound according to claim 3, in which R ⁵ in R ⁵ , R ⁶ -aminocarbonyl group is C _1-4 alkoxycarbonyl C _1-4 alkyl and R ⁶ is N. 6. The compound according to claim 3, in which R ⁵ in the R ⁵ , R ⁶ -aminocarbonyl group is a C _1-9 heteroaryl C _1-4 alkyl, wherein the (hetero) aryl group is optionally substituted with one or more substituents selected from hydroxy, amino , halogen, nitro, trifluoromethyl, cyano, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _1-4 (di) alkylamino or C _1-4 alkoxycarbonyl C _1-4 alkyl and R ⁶ is N. 7. The compound according to claims 1-6, in which X is CH ₂ . 8. The compound according to claims 1-6, in which R ¹ is C _1-6 alkyl, phenyl or C _1-5 heteroaryl. 9. The compound according to claims 1-6, in which R ² , R ³ are halogen or C _1-4 alkoxygroup. 10. The compound according to claims 1-6 for use in therapy. 11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9, including 2-methyl-5-oxo-7-phenyl-4- (3,4,5-trimethoxyphenyl) -1,4,5,6,7 , 8-hexahydroquinoline-3-carbonitrile and pharmaceutically acceptable excipients. 12. The use of the compounds according to any one of claims 1 to 9, including 2-methyl-5-oxo-7-phenyl-4- (3,4,5-trimethoxyphenyl) -1,4,5,6,7,8- hexahydroquinoline-3-carbonitrile, or a pharmaceutically acceptable salt thereof, or a solvate thereof, for the manufacture of a medicament for the treatment of impaired fertility.