Selective and potent adenosine A3 receptor antagonists by methoxyaryl substitution on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold

Eur J Med Chem. 2013 Jan;59:235-42. doi: 10.1016/j.ejmech.2012.11.010. Epub 2012 Nov 24.


The influence of diverse methoxyphenyl substitution patterns on the N-(2,6-diarylpyrimidin-4-yl)acetamide scaffold is herein explored in order to modulate the A(3) adenosine receptor antagonistic profile. As a result, novel ligands exhibiting excellent potency (K(i) on A(3) AR < 20 nM) and selectivity profiles (above 100-fold within the adenosine receptors family) are reported. Moreover, our joint theoretical and experimental approach allows the identification of novel pharmacophoric elements conferring A(3)AR selectivity, first established by a robust computational model and thereafter characterizing the most salient features of the structure-activity and structure-selectivity relationships in this series.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / chemistry
  • Adenosine A3 Receptor Antagonists / chemistry*
  • Anisoles / chemical synthesis*
  • Anisoles / chemistry
  • Binding Sites
  • Computer Simulation*
  • Humans
  • Models, Molecular
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Structure-Activity Relationship


  • Acetamides
  • Adenosine A3 Receptor Antagonists
  • Anisoles
  • Pyrimidines
  • acetamide
  • anisole