Synthesis and Biological Evaluation of Novel 1-Deoxy-1-6-((hetero)arylcarbonyl)hydrazino-9H-purin-9-yl-N-ethyl-beta-D-ribofuranuronamide Derivatives as Useful Templates for the Development of A_(2B) Adenosine Receptor Agonists

摘要

The lack of molecules endowed with selective and potent agonistic activity toward the hA_(2B) adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential.We report the design and the synthesis of the first potent (EC_(50) in the nanomolar range) and selective hA_(2B) adenosine receptor agonists consisting of 1-deoxy-1-6-((hetero)arylcarbonyl)-hydrazino-9H-purin-9-yl-N-ethyl-beta-D-ribofuranuronamide derivatives.The concurrent effect of 6-substitution of the purine nucleus with a ((hetero)arylcarbonyl)hydrazino function and a 2-chloro substitution has been investigated in such NECA derivatives.