Design, synthesis, and biological evaluation of novel 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines as adenosine A1 receptor antagonists Original Research Article

A series of 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines have been synthesized and evaluated for their adenosine A1 receptor inhibitory activity in the radioligand binding assays. The compounds were tested for the inhibition percent (IP) and the affinity toward A1AR (Ki) that IP were more than 90% in the nanomolar range. 4-Cyclopentylamino-7,8-dichloro-1-hydroxymethylimidazo[1,2-a]quinoxaline 18 is the most potent compound in this series, having Ki = 7 nM, which is remarkably higher than that of IRFI-165 (Ki = 48). 1-Hydroxymethyl groups of the tricyclic heteroarmatic compounds displayed the potent affinities toward A1AR.