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

  • Bioorg Med Chem Lett. 2011 May 15;21(10):2898-905. doi: 10.1016/j.bmcl.2011.03.073.
Siew Lee Cheong  1 ,  Stephanie Federico ,  Gopalakrishnan Venkatesan ,  Priyankar Paira ,  Yi-Ming Shao ,  Giampiero Spalluto ,  Chun Wei Yap ,  Giorgia Pastorin
Affiliations
  • 1. Department of Pharmacy, National University of Singapore, 3 Science Drive 2, Block S15, #05-PI-03, Singapore 117543, Singapore.
PMID: 21511471 DOI: 10.1016/j.bmcl.2011.03.073
Abstract

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.

Products