Patent EA-002352-B1 (EA)
Title: Indazole amide compounds as serotoninergic agents
Inventor: ALISI ALESSANDRA
IPC: C07D401/12
Filed: 1998-04-02
Abstract: 1. A compound having the general formula   wherein R6 is selected from the group consisting of, phenyl C1-3 alkyl, C3-7 cycloalkyl, heterocyclic ring having from 5 to 6 members where 1 to 2 members are heteroatoms, the same or different from each other, selected from the group consisting of N and O, dimethylamino C1-3 alkyl, methoxy C1-3 alkyl, aminosulphonylmethyl and aryl substituted by hydroxy; acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof. 2. The compound according to claim 1, wherein the heterocyclic ring is selected from the group consisting of furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, furazanyl, pyrrolinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, morpholinyl. 3. The compound according to claim 1, wherein R6 is selected from the group consisting of cyclopropyl, cyclohexyl, pyridinyl, tetrazolyl, morpholinyl, methoxymethyl, methexypropyl, hydroxyphenyl, dimethylaminomethyl and aminosulphonylmethyl. 4. The compound according to claim 1, wherein R6 is cyclohexyl. 5. The compound according to claim 1, wherein R6 is pyridinyl. 6. The compound according to claim 1, wherein R6 is dimethylaminomethyl. 7. The compound according to claim 1, wherein R6 is morpholinyl. 8. The compound according to claim 1, wherein R6 is aminosulphonylmethyl. 9. A process for preparing a compound of the formula (I), acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof, comprising: a) acylating a 4-aminomethyl piperidine of the formula:   wherein P is a benzoyl group by means of a 1-alkyl-indazole-3-carboxylic acid halide of the formula:   wherein X is halogen, to give a compound of the formula:   b) de-protecting a compound of the formula (IV) to give a compound of the formula:   c) alkylating a compound of the formula (V) with a compound of the formula (VI) to give a compound of the formula (I) according to the following reaction scheme:   wherein R6 is as defined above, and  Y is halogen, d) optionally forming an acid addition salt of an indazole amide compound of the formula (I) with a pharmaceutically acceptable organic or inorganic acid, or a pharmaceutically acceptable quaternary salt of an indazole amide compound of the formula (I). 10. The process according to claim 9, wherein step a) is carried out by reacting a compound of the formula (II) with a compound of the formula (III) in which X is chlorine, in the presence of a diluent and at a temperature of from 0 to 140 degree C. for a period of time of from 0.5 to 20 hours. 11. The process according to claim 9, wherein step b) is carried out by catalytic hydrogenation. 12. The process according to claim 9 wherein when in a compound of the formula (VI), Y is chlorine or bromine, step c) is performed in the presence of an acceptor of acids and in the presence of a diluent. 13. A pharmaceutical composition, wherein said composition comprises an effective dose of at least one compound of the formula:   wherein R6 is selected from the group consisting of, phenyl C1-3 alkyl, C3-7 cycloalkyl, heterocyclic ring having from 5 to 6 members where 1 to 2 members are heteroatoms, the same or different from each other, selected from the group consisting of N and O, dimethylamino C1-3 alkyl, methoxy C1-3 alkyl, aminosulphonylmethyl and aryl substituted by hydroxy; acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof.