Pharmacophore elucidation for a new series of 2-aryl-pyrazolo-triazolo-pyrimidines as potent human A3 adenosine receptor antagonists.

A ligand-based pharmacophore was obtained for a new series of 2-unsubstituted and 2-( para -substituted)phenyl-pyrazolo-triazolo-pyrimidines as potent human A 3 adenosine receptor antagonists. Through comparative molecular field analysis-based quantitative structure–activity relationship studies, structural features at the N 5 -, N 8 - and C 2 -positions of the tricyclic nucleus were deeply investigated, with emphasis given to the unprecedentedly explored C 2 -position. The resulting model showed good correlation and predictability ( r 2  = 0.936; q 2  = 0.703; r pred 2 = 0.663 ). Overall, the contribution of steric effect was found relatively more predominant for the optimal interaction of these antagonists to the human A 3 receptor.