Patent RU-2319692-C2 (RU)
Title: Derivatives of tetrahydrocarbazole, method for preparing tetrahydrocarbazole (variants), their using (variants) and pharmaceutical composition possessing activity of antagonist of gonadotropin-releasing hormone (variants)
Inventor: KOPPITS MARKUS
IPC: C07D209/88
Filed: 2002-12-16
Granted: 2008-03-20
Abstract: FIELD: organic chemistry, medicine, pharmacy. 
     SUBSTANCE: invention relates to novel derivatives of tetrahydrocarbazole of the general formula (I):   wherein R 1  means hydrogen atom (H), (C 1 -C 6 )-alkyl and can be optionally substituted with groups aryl, heteroaryl or -COOR 11  wherein aryl or heteroaryl can be substituted with up to three substitutes that are chosen independently from group comprising -NO 2 , -CH 3 , -CF 3 , -OCH 3 , -OCF 3  and halogen atoms; R 11  means H, (C 1 -C 12 )-alkyl, (C 1 -C 12 )-aralkyl, aryl, heteroaryl, -COCH 3  and can be optionally substituted with one substitute chosen from group comprising -CONH 2 , -COCH 3 , -COOCH 3 , -SO 2 CH 3  and aryl; each R 2 , R 3 , R 4  and R 5  means independently H, halogen atom, -COOH, - CONH 2 , -CF 3 , -OCF 3 , -NO 2 , (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy group, (C 1 -C 12 )-aralkyl, aryl, heteroaryl; R 6  means -CONR 8 R 9 , -COOR 8 , -CH 2 NR 8 R 9 , -CH 2 R 8 , -CH 2 OR 8 ; each R 8  and R 9  means independently H, (C 1 -C 12 )-alkyl, (C 1 -C 12 )-aralkyl, (C 1 -C 12 )-heteroaryl, aryl or heteroaryl wherein each of them can be with one or more substitutes chosen from group comprising -OH, -NH 2 , -CONHR 10 , -COOR 10 , -NH-C(=NH)-NH 2  and halogen atom and wherein R 10  means H, (C 1 -C 12 )-alkyl, (C 1 -C 12 )-aralkyl, aryl or heteroaryl and it is substituted optionally with group -CON(R 11 ) 2 , or wherein radicals R 8  and R 9  in common with nitrogen atom to which they are bound form heterocyclic structure; R 7  means H, (C 1 -C 12 )-alkyl, (C 1 -C 12 )-aralkyl, aryl or heteroaryl, -NR 12 R 13 , -NHCOR 14 , -NHCONHR 14 , -NHCOOR 14 , -NHSO 2 R 14  and can be substituted optionally with one or more substitutes chosen from group comprising -OH, -NH 2 , -CONH 2 , -COOH and halogen atom; each among R 12  and R 13  means independently H, (C 1 -C 12 )-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 -NO 2 , -CH 3 , -CF 3 , -OCH 3 , -OCF 3  and halogen atom; R 14  means H, (C 1 -C 12 )-alkyl, (C 1 -C 12 )-aralkyl, aryl or heteroaryl that can be substituted optionally with one or more substitutes chosen from group comprising -NO 2 , -CH 3 , -OR 11 , -CF 3 , -OCF 3 , -OH, -N(R 11 ) 2 , -OCOR 11 , -COOH, -CONH 2 , -NHCONHR 11 , -NHCOOR 11  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, -CONH 2 , -CF 3 , -OCF 3 , -NO 2 , (C 1 -C 6 )-alkyl, (C 1 -C 6 )-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