ISOQUINOLINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF IN THE TREATMENT OF MELATONINERGIC SYSTEM PROBLEMS

摘要

Isoquinoline derivatives (I) are new. Isoquinoline derivatives of formula (I) and their isomers and salts are new. [Image] n : 1-3; A : NR-CZ-R', CZ-NRR' or NR-CZ-NR'R; Z : O or S; R : H or 1-6C alkyl; R' : 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, 3-8C cycloalkyl, (3-8C)cycloalkyl(1-6C)alkyl, aryl, aryl(1-6C)alkyl, heteroaryl or heteroaryl(1-6C)alkyl; X : N or NR 1; R 1H, 1-6C alkyl, 3-8C cycloalkyl, (3-8C)cycloalkyl(1-6C)alkyl, aryl, aroyl, aryl(1-6C)alkyl, heteroaryl, heteroaroyl or heteroaryl(1-6C)alkyl; R 21-6C alkoxy, 3-8C cycloalkoxy or (3-8C)cycloalkyl(1-6C)alkoxy; aryl : phenyl or naphthyl optionally substituted with 1-3 of 1-6C alkyl, 1-6C alkoxy, OH, COOH, alkoxycarbonyl, CHO, NO 2, CN, hydroxymethyl, NH 2, mono- or di(1-6C alkyl)amino or halo; heteroaryl : a 5- to 10-membered mono- or bicyclic group with 1-3 heteroatoms (O, S or N), optionally substituted with 1-3 of 1-6C alkyl, 1-6C alkoxy, OH, COOH, alkoxycarbonyl, CHO, NO 2, CN, hydroxymethyl, NH 2, mono- or di(1-6C alkyl)amino or halo. An independent claim is also included for a process for preparing (I). ACTIVITY : Tranquilizer; Antidepressant; Vasotropic; Neuroleptic; Anorectic; Anticonvulsant; Antidiabetic; Antiparkinsonian; Neuroprotective; Nootropic; Antimigraine; Cerebroprotective; Cytostatic; Immunomodulator. In a forced swimming test, oral administration of N-(2-(6-methoxy-4-isoquinolinyl)ethyl)acetamide hydrochloride (2.5 mg/kg) to unspecified animals reduced the immobilization time from 102 seconds (control) to 57 seconds. MECHANISM OF ACTION : Melatonin receptor ligand.