CoMFA, Synthesis, and Pharmacological Evaluation of (E)-3-(2-Carboxy-2-arylvinyl)-4, 6-dichloro-1 H-indole-2-carboxylic Acids: 3-[2-(3-Aminophenyl)-2-carboxyvinyl] …

…, D Matthews, TC McCloskey, S Meikrantz…

Index: Baron, Bruce M.; Cregge, Robert J.; Farr, Robert A.; Friedrich, Dirk; Gross, Raymond S.; Harrison, Boyd L.; Janowick, David A.; Matthews, Donald; McCloskey, Timothy C.; Meikrantz, Scott; Nyce, Philip L.; Vaz, Roy; Metz, William A. Journal of Medicinal Chemistry, 2005 , vol. 48, # 4 p. 995 - 1018

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Citation Number: 24

Abstract

(E)-3-(2-Carboxy-2-phenylvinyl)-4, 6-dichloro-1 H-indole-2-carboxylic acid, 1, is a potent and selective antagonist of the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Using 3D comparative molecular field analysis (CoMFA) to guide the synthetic effort, a series of aryl diacid analogues of 1 were synthesized to optimize in vivo potency, duration of action, and binding activity. It was found that the incorporation of a substituted aromatic ...