ChemInform Abstract: Syntheses of Biphenyl Analogues of AP7, a New Class of Competitive N‐ Methyl‐D‐aspartate (NMDA) Receptor Antagonists.

Abstract

Syntheses of a series of enantiomerically pure, substituted analogues 7b-t of SDZ EAR 51 5 (7a) were described (Schemes I and 2). Affinities for the NMDA receptor were measured ((3H]CGP-39653 binding assay) and competitive NMDA antagonistic potencies determined in a functional test (rat neocortical slice preparation). Structure-activity relationships show that attachment of an OH group at position 4 of the chain-inserted benzene ring of the biphenyl moiety and/or expansion of the angle between the planes of the two benzene rings by ortho-substituents increase in vifro activities into the low nanomolar range.