Design, synthesis, and biological evaluation of novel 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines as adenosine A(1) receptor antagonists.
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)=7nM, 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.
Liu
Chun-He
CH
No. 7 Department, Beijing Institute of Pharmacology and Toxicology Academy, 27 Taiping Road, Beijing 100850, PR China. liuhe@nic.bmi.ac.cn
Wang
Bo
B
Li
Wei-Zhang
WZ
Yun
Liu-Hong
LH
Liu
Ying
Y
Su
Rui-Bing
RB
Li
Jin
J
Liu
He
H
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D006571:Heterocyclic Compounds / Q000737:chemistry; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D058916:Adenosine A1 Receptor Antagonists; D006571:Heterocyclic Compounds; D011810:Quinoxalines