Heterocyclic compounds

Claim 1

Indole derivatives of the following general formula: wherein R is phenyl, optionally substituted with halogen, lower alkyl or trifluoromethyl, or a hetero aromatic group, such as 2-thienyl, 3-thienyl, 2-furoyl, 3- furoyl, 2-thiazol, 2-oxazol, 2-imidazole, 2-pyridyl, 3-pyridyl or 4-pyridyl; R is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, lower alkylthio, trifluoromethyl,lower alkylsulfonyl, amino, lower alkylamino or lower di-alkylamino; "A" is nitrogen or carbon, and the dotted line indicates - when A is carbon - an optional bond; R 2 is hydrogen, cycloalkyl, lower alkyl or lower alkenyl, optionally substituted with one or two hydroxy groups, any hydroxy group present being optionally esterified with an aliphatic carboxylic acid radical having from two to twenty-four carbon atoms inclusive, or R 2 is the group wherein "n" is an integer of 2-6; X is oxygen or sulfur, or> C = X may constitute the group = when Y is =N- or =CH-; Y is oxygen, sulfur, CH 2 or N R 3 , where R is hydrogen or lower alkyl, lower alkenyl or a cycloalkylmethyl group, said "cycloalkyl" having from three to six carbon atoms inclusive; Z is -(CH 2 ) m -, "m" being 2 or 3, or Z is -CH=CH- or 1,2-phenylene optionally substituted with halogen or trifluoromethyl, or Z is -CO(or S)CH 2 -; U is nitrogen or carbon, provided that when R is chloro, A is nitrogen and R 2 is methyl or cyclohexyl, R may not be phenyl; as well as their pharmaceutically acceptable acid addition salts.

Claim 3

A method for the preparation of an indole derivative of the following general formula: wherein R is phenyl, optionally substituted with halogen, lower alkyl or trifluoromethyl, or a hetero aromatic group, such as 2-thienyl, 3-thienyl, 2-furoyl, 3- furoyl, 2-thiazol, 2-oxazol, 2-imidazole, 2-pyridyl, 3-pyridyl or 4-pyridyl; R is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, lower alkylthio, trifluoromethyl,lower alkylsulfonyl, amino, lower alkylamino or lower di-alkylamino; "A" is nitrogen or carbon, and the dotted line indicates - when A is carbon - an optional bond; R 2 is hydrogen, cycloalkyl, lower alkyl or lower alkenyl, optionally substituted with one or two hydroxy groups, any hydroxy group present being optionally esterified with an aliphatic carboxylic acid radical having from two to twenty-four carbon atoms inclusive, or R 2 is the group wherein "n" is an integer of 2-6; X is oxygen or sulfur, or> C = X may constitute the group = when Y is =N- or =CH-; Y is oxygen, sulfur, CH 2 or N R 3 , where R is hydrogen or lower alkyl, lower alkenyl or a cycloalkylmethyl group, said "cycloalkyl" having from three to six carbon atoms inclusive; Z is -(CH 2 ) m -, "m" being 2 or 3, or Z is -CH=CH- or 1,2-phenylene optionally substituted with halogen or trifluoromethyl, or Z is -CO(or S)CH 2- ; U is nitrogen or carbon, provided that when R is chloro, A is nitrogen and R 2 is methyl or cyclohexyl, R may not be phenyl; as well as their pharmaceutically acceptable acid addition salts, which comprises a) reacting an indole derivative of the following formula: wherein R and R are as defined above, with a 4-piperidone of the formula: wherein R 2 is as defined above, or b) reducing a compound of the following formula: wherein R 1 , R and R 2 are as defined above, or c) reacting a compound of the following formula: wherein R 1 , R2and A are as defined above, with a compound of formula: wherein R is as defined above and "hal" is halogen, in the presence of a metal catalyst, or d) reacting a compound of the following formula: wherein R 1 , R and A are as defined above, with a lower alkyl halide or an epoxide of formula wherein R is hydrogen, methyl or ethyl, or e) reducing a compound of the following formula: wherein R 1 , R and A are as defined above and R 4 is hydrogen, lower alkyl (1-3 C-atoms) or lower alkoxy (1-3 C-atoms), or f) heating a compound of the following formula: wherein R and R are as defined above, with a piperazine of formula: wherein R 2 is as defined above, or g) reducing a compound of the following formula: wherein R 1 , R and R are as defined above, with a suitable reducing agent, whereupon the indole of Formula I is isolated in the form of the free base or a pharmaceutically acceptable acid addition salt thereof, and if the group R 2 contains one or two hydroxyl groups, if desired, acylating such a hydroxy group with a reactive derivative of an aliphatic carboxylic acid having from two to twenty-four carbon atoms, and isolating the ester formed as the free base or a pharmaceutically acceptable acid addition salt thereof.