1,2,4-Triazolo[1,5-a]quinoxaline derivatives: synthesis and biological evaluation as adenosine receptor antagonists

Since most of the reported adenosine receptor antagonists are 2-(hetero)aryl-substituted tricyclic heteroaromatic derivatives, in the present study we report the synthesis and the biological evaluation of a new set of 4-amino-1,2,4-triazolo[1,5-a]quinoxalines containing at position-2 an ethyl carboxylate group or a hydrogen atom. The structure-activity relationships on these compounds were in accordance with those of a previously reported series of analogous size and shape, thus suggesting a similar A(1)-binding mode. In particular, the binding data indicate that alkylation of the 4-amino group of these derivatives lead to potent A(1)-receptor antagonists. Moreover, as new results, this study has pointed out that the ethyl 2-carboxylate group can advantageously replace the 2-(hetero)aryl ring of previously reported triazoloquinoxaline derivatives, affording an ameliorated interaction with the A(1)-receptor subtype.