136125-89-8Relevant academic research and scientific papers
CoMFA, synthesis, and pharmacological evaluation of (E)-3-(2-carboxy-2- arylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acids: 3-[2-(3-Aminophenyl)-2- carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, a potent selective glycine-site NMDA receptor antagonist
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.
, p. 995 - 1018 (2007/10/03)
(E)-3-(2-Carboxy-2-phenylvinyl)-4,6-dichloro-1H-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 with an electron withdrawing group or a heterocyclic group at the 2-position of the 3-propenyl moiety of 1 gave compounds with better affinity and potency in the murine stroke model. Ultimately this led to the discovery of 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, 19, as a new potent selective glycine-site NMDA receptor antagonist.
