SYNTHESES OF BIPHENYL ANALOGS OF AP7, A NEW CLASS OF COMPETITIVE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ANTAGONISTS

Syntheses of a series of enantiomerically pure, substituted analogues 7b-t of SDZ EAB 515 (7a) were described (Schemes I and 2). Affinities for the NMDA receptor were measured ([H-3]CGP-39653 binding assay) and competitive NMDA antagonistic potencies determined in a Functional te st (rat neocortical slice preparation). Structure-activity relationshi ps show that attachment of an OH group at position 4 of the chain-inse rted benzene ring of the biphenyl moiety and/or expansion of the angle between the planes of the two benzene rings by ortho-substituents inc rease in vitro activities into the low nanomolar range.