4-Hydroxy-1-[2-(4-hydroxyphenoxy) ethyl]-4-(4-methylbenzyl) piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist

…, CS Konkoy, SA Espitia, M Tran, DM Rock…

Index: Zhou, Zhang-Lin; Cai, Sui Xiong; Whittemore, Edward R.; Konkoy, Christopher S.; Espitia, Stephen A.; Tran, Minhtam; Rock, David M.; Coughenour, Linda L.; Hawkinson, Jon E.; Boxer, Peter A.; Bigge, Christopher F.; Wise, Lawrence D.; Weber, Eckard; Woodward, Richard M.; Keana, John F. W. Journal of Medicinal Chemistry, 1999 , vol. 42, # 15 p. 2993 - 3000

Full Text: HTML

Citation Number: 45

Abstract

A structure-based search and screen of our compound library identified N-(2-phenoxyethyl)- 4-benzylpiperidine (8) as a novel N-methyl-d-aspartate (NMDA) receptor antagonist that has high selectivity for the NR1/2B subunit combination (IC50= 0.63 μM). We report on the optimization of this lead compound in terms of potency, side effect liability, and in vivo activity. Potency was assayed by electrical recordings in Xenopus oocytes expressing ...