New N-(piperidinyl)(phenyl)methyl benzamide derivatives are glycine transport inhibitors, useful for the treatment of e.g. dementia-associated behavioral problems, psychoses, anxiety, depression and alcohol abuse

摘要

N-(piperidinyl)(phenyl)methyl benzamide derivatives (I), are new. N-(piperidinyl)(phenyl)methyl benzamide derivatives of formula (I) and their acid addition salts are new. [Image] R 1 : H, 1-7C alkyl (optionally fluorinated), 3-7C cycloalkyl, (3-7C)cycloalkyl(1-3C)alkyl, phenyl(1-3C)alkyl (optionally substituted by 1 or 2 OMe), 2-4C alkenyl or 2-4C alkynyl; R 2 : 1-7C alkyl, 3-7C cycloalkyl or (3-7C)cycloalkyl(1-3C)alkyl; X : H, halo, CF 3, 1-6C alkyl or 1-6C alkoxy; R 3 : H, halo, CF 3, 1-6C alkyl, 3-7C cycloalkyl, 1-6C alkoxy, phenyl, CN, acetyl, benzoyl, 1-6C alkylthio, 1-6C alkylsulfonyl, COOH, 1-6C alkoxycarbonyl, NR 4R 5, SO 2NR 4R 5 or CONR 4R 5, and R 4, R 5 : H, 1-6C alkyl or 3-7C cycloalkyl, or NR 4R 5 : pyrrolidino, piperidino or morpholino. ACTIVITY : Nootropic; Neuroleptic; Tranquilizer; Antidepressant; Antialcoholic; Antimigraine; Relaxant; Analgesic; Antiparkinsonian; Anticonvulsant; Neuroprotective. MECHANISM OF ACTION : Glycine transporter inhibitor. In a test, the most active compounds (I) (unspecified) exhibited IC 50 values of 0.001-10 MicroM against glycine uptake by SK-N-MC cells expressing native human glycine transporter glyt1.