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

The synthesis and glycine/NMDA and AMPA receptor affinities of a set of eth yl (+/-) 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-hexahydroimi dazo[1,5-a]quinoxaline 1,3,4-triones 12-24 are reported. Compounds 1-11 bea r a side-chain at position 1 which has been spatially constrained in compou nds 12-24. Most of the reported tricyclic derivatives 12-24 showed glycine/ NMDA binding activity comparable to that of their corresponding bicyclic an alogues 1-11 providing further evidence that the spatial orientation of the side-chain is an important structural requirement for glycine/NMDA recepto r antagonists. (C) 2001 Editions scientifiques et medicales Elsevier SAS.