Structure activity relationship of 2-arylalkynyl-adenine derivatives as human A₃ adenosine receptor antagonists.

ABSTRACT: Recognition of nucleosides at adenosine receptors (ARs) is supported by multiple X-ray structures, but the structure of an adenine complex is unknown. We examined the selectivity of predicted A₁AR and A₃AR adenine antagonists that incorporated known agonist affinity-enhancing N ⁶ and C2 substituents. Adenines with A₁AR-favoring N ⁶-alkyl, cycloalkyl and arylalkyl substitutions combined with an A₃AR-favoring 2-((5-chlorothiophen-2-yl)ethynyl) group were human (h) A₃AR-selective, e.g. MRS7497 17 (∼1000-fold over A₁AR). In addition, binding selectivity over hA_2AAR and hA_2BAR and functional A₃AR antagonism were demonstrated. 17 was subjecte

SUBMITTER: Yu J 

PROVIDER: S-EPMC6256369 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature