Synthesis and structure-activity relationships of a series of 2-alkynyl-NECA derivatives as selective A2 adenosine receptor agonist

A series of new 2-alkynyl derivs. of NECA and of N-ethyl-1'-deoxy-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-β-D-ribofuranuronamide were studies in binding and functional assays to assess their potency for the A2 compared to the A1 adenosine receptor. The results indicate that the 2-alkynyl-NECA derivs. are selective A2 agonists possessing inhibitory actions on platelet aggregation. Structure-activity relations are discussed in relation to A2 receptor selectivity and platelet aggregation inhibition. The hydrophobicity index of the compds. is only slightly correlated with the binding data, whereas compds. with high hydrophobicity index had decreased platelet aggregation inhibitory activity.