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

Abstract A series of 4-alkylamino-1-hydroxymethylimidazo[1,2- a ]quinoxalines have been synthesized and evaluated for their adenosine A 1 receptor inhibitory activity in the radioligand binding assays. The compounds were tested for the inhibition percent (IP) and the affinity toward A 1 AR ( K i ) 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 K i  = 7 nM, which is remarkably higher than that of IRFI-165 ( K i  = 48). 1-Hydroxymethyl groups of the tricyclic heteroarmatic compounds displayed the potent affinities toward A 1 AR.