title: Design, synthesis, and biological evaluation of novel 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines as adenosine A(1) 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)=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.
authors.affiliation: No. 7 Department, Beijing Institute of Pharmacology and Toxicology Academy, 27 Taiping Road, Beijing 100850, PR China. liuhe@nic.bmi.ac.cn
authors.forename: Chun-He
authors.initials: CH
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Wei-Zhang
authors.initials: WZ
authors.lastname: Li
authors.forename: Liu-Hong
authors.initials: LH
authors.lastname: Yun
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Rui-Bing
authors.initials: RB
authors.lastname: Su
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: He
authors.initials: H
authors.lastname: Liu
mesh_terms: 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
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D006571:Heterocyclic Compounds; D011810:Quinoxalines