DERIVATIVES OF TETRAHYDROCARBAZOLE, METHOD FOR PREPARING TETRAHYDROCARBAZOLE (VARIANTS), THEIR USING (VARIANTS) AND PHARMACEUTICAL COMPOSITION POSSESSING ACTIVITY OF ANTAGONIST OF GONADOTROPIN-RELEASING HORMONE (VARIANTS) Russian patent published in 2008 - IPC C07D209/82 A61K31/403 A61P15/16 A61P15/18 

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of tetrahydrocarbazole of the general formula (I): wherein R¹ means hydrogen atom (H), (C₁-C₆)-alkyl and can be optionally substituted with groups aryl, heteroaryl or -COOR¹¹ wherein aryl or heteroaryl can be substituted with up to three substitutes that are chosen independently from group comprising -NO₂, -CH₃, -CF₃, -OCH₃, -OCF₃ and halogen atoms; R¹¹ means H, (C₁-C₁₂)-alkyl, (C₁-C₁₂)-aralkyl, aryl, heteroaryl, -COCH₃ and can be optionally substituted with one substitute chosen from group comprising -CONH₂, -COCH₃, -COOCH₃, -SO₂CH₃ and aryl; each R², R³, R⁴ and R⁵ means independently H, halogen atom, -COOH, - CONH₂, -CF₃, -OCF₃, -NO₂, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy group, (C₁-C₁₂)-aralkyl, aryl, heteroaryl; R⁶ means -CONR⁸R⁹, -COOR⁸, -CH₂NR⁸R⁹, -CH₂R⁸, -CH₂OR⁸; each R⁸ and R⁹ means independently H, (C₁-C₁₂)-alkyl, (C₁-C₁₂)-aralkyl, (C₁-C₁₂)-heteroaryl, aryl or heteroaryl wherein each of them can be with one or more substitutes chosen from group comprising -OH, -NH₂, -CONHR¹⁰, -COOR¹⁰, -NH-C(=NH)-NH₂ and halogen atom and wherein R¹⁰ means H, (C₁-C₁₂)-alkyl, (C₁-C₁₂)-aralkyl, aryl or heteroaryl and it is substituted optionally with group -CON(R¹¹)₂, or wherein radicals R⁸ and R⁹ in common with nitrogen atom to which they are bound form heterocyclic structure; R⁷ means H, (C₁-C₁₂)-alkyl, (C₁-C₁₂)-aralkyl, aryl or heteroaryl, -NR¹²R¹³, -NHCOR¹⁴, -NHCONHR¹⁴, -NHCOOR¹⁴, -NHSO₂R¹⁴ and can be substituted optionally with one or more substitutes chosen from group comprising -OH, -NH₂, -CONH₂, -COOH and halogen atom; each among R¹² and R¹³ means independently H, (C₁-C₁₂)-alkyl and can be substituted optionally with one or more substitutes chosen from aryl, heteroaryl that in turn can comprise up to three substitutes chosen independently from -NO₂, -CH₃, -CF₃, -OCH₃, -OCF₃ and halogen atom; R¹⁴ means H, (C₁-C₁₂)-alkyl, (C₁-C₁₂)-aralkyl, aryl or heteroaryl that can be substituted optionally with one or more substitutes chosen from group comprising -NO₂, -CH₃, -OR¹¹, -CF₃, -OCF₃, -OH, -N(R¹¹)₂, -OCOR¹¹, -COOH, -CONH₂, -NHCONHR¹¹, -NHCOOR¹¹ and halogen atom; each radical among R^a, R^b, R^c, R^d, R^e and R^f means independently H, halogen atom, -COOH, -CONH₂, -CF₃, -OCF₃, -NO₂, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy group, aryl or heteroaryl wherein heteroaryl and heterocyclic group if it presents means pyridinyl, pyrrolidinyl, indolyl and under condition that compound of the general formula (I) is not chosen from group comprising 3-amino-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 3-amino-6-methoxy-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 3-amino-6-benzyloxy-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 3-acetamido-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 3-acetamido-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid methyl ester, 3-acetamido-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid (-)-menthyl ester, 3-tert.-butoxycarbonylamino-1,2,3,4-tetrahydrocarbazole 3-carboxylic acid, 9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxylic acid, 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxylic acid, 9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxamide, 6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole 4-carboxamide. Compounds possess activity of antagonist of gonadotropin-releasing hormone that allows their using in pharmaceutical compositions. Also, invention describes methods for synthesis of these compounds.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

22 cl, 1 tbl, 32 ex