Synthesis of a set of ethyl 1-carbamoyl-3-oxoquinoxaline-2-carboxylates and of their constrained analogue imidazo[1,5-a]quinoxaline-1,3,4-triones as glycine/NMDA receptor antagonists

Abstract The synthesis and glycine/NMDA and AMPA receptor affinities of a set of ethyl (±) 1- N -carbamoyl-1,2,3,4-tetrahydro-3-oxoquinoxaline-2-carboxylates 1 – 11 and those of their constrained analogue (±) 1,2,3,3a,4,5-hexahydroimidazo[1,5-a]quinoxaline-1,3,4-triones 12 – 24 are reported. Compounds 1 – 11 bear a side-chain at position 1 which has been spatially constrained in compounds 12 – 24 . Most of the reported tricyclic derivatives 12 – 24 showed glycine/NMDA binding activity comparable to that of their corresponding bicyclic analogues 1 – 11 providing further evidence that the spatial orientation of the side-chain is an important structural requirement for glycine/NMDA receptor antagonists.