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. Epub 2011 Mar 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A3 Receptor Antagonists* / chemistry
  • Adenosine A3 Receptor Antagonists* / pharmacology
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Binding / drug effects
  • Pyrazoles / chemistry*
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology
  • Quantitative Structure-Activity Relationship
  • Triazoles / chemistry*


  • Adenosine A3 Receptor Antagonists
  • Pyrazoles
  • Pyrimidines
  • Triazoles
  • pyrazole