| 摘要 |
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 Ra, Rb, Rc, Rd, Re and Rf 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 |
