4,5-dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones: Excitatory amino acid antagonists with combined glycine NMDA and AMPA receptor affinity

A series of 4,5-dihydro-1,2,4-triazolo[1,5-alpha]quinoxalin-4-ones bearing different substituents on the benzo-fused ring and at position 2 were synth esized and biologically evaluated for their binding at glycine/NMDA and AMP A receptors. Most of the reported compounds show combined glycine/NMDA and AMPA receptor binding activity providing further evidences of the structura l similarities of the binding pockets of both receptor recognition sites. M oreover, this study has pointed out some differences for the binding at eac h receptor type. In particular, for the glycine/NMDA receptor-ligand intera ction, the presence of a free acidic function at position 2 and an electron -withdrawing substituent(s) nonbulkier than chlorine atom(s) on the benzo-f used moiety is required. Functional antagonism at the NMDA receptor-ion cha nnel complex was also performed on some selected compounds.