Design, synthesis, SAR, and biological evaluation of highly potent benzimidazole-spaced phosphono-α-amino acid competitive NMDA antagonists of the AP-6 type

…, AH Katz, JA Moyer, M Abou-Gharbia

Index: Baudy; Fletcher III; Yardley; Zaleska; Bramlett; Tasse; Kowal; Katz; Moyer; Abou-Gharbia Journal of Medicinal Chemistry, 2001 , vol. 44, # 10 p. 1516 - 1529

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Citation Number: 35

Abstract

A series of 2-amino-(phosphonoalkyl)-1 H-benzimidazole-2-alkanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H] TCP binding assay and in vivo by employing an NMDA-induced seizure model. Several compounds of the AP-6 type demonstrated potent and selective NMDA antagonistic ...