New N-piperidinylmethyl benzamide derivatives useful as glycine transporter inhibitors, e.g. for treating dementia-associated behavioral problems, psychoses, anxiety, depression, alcohol abuse

摘要

N-Piperidinylmethyl benzamide derivatives (I) are new. N-Piperidinylmethyl benzamide derivatives of formula (I) and their acid addition salts, hydrates and solvates are new. [Image] R 1H, 1-7C alkyl (optionally fluorinated), 3-7C cycloalkyl, (3-7C)cycloalkyl(1-3C)alkyl, phenyl(1-3C)alkyl (optionally mono- or disubstituted with OMe), 2-4C alkenyl or 2-4C alkynyl; R 2pyridyl, furyl, thienyl, thiazolyl or oxazolyl, all optionally substituted with halo, CF 3, 1-6C alkyl and 1-6C alkoxy; R 3H, 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; R 4, R 5H, 1-6C alkyl or 3-7C cycloalkyl, or NR 4R 5 is pyrrolidino, piperidino or morpholino. ACTIVITY : Nootropic; Neuroleptic; Tranquilizer; Antidepressant; Antialcoholic; Antimigraine; Relaxant; Analgesic; Antiparkinsonian; Anticonvulsant; Neuroprotective. MECHANISM OF ACTION : Glycine transporter inhibitor. The most active compounds (unspecified) have IC50 values of 0.001-1 MicroM against glycine uptake by SK-N-MC cells expressing native human glycine transporter glyt1.