Effect of Nitrogen Atom Substitution in A3 Adenosine Receptor Binding: N‑(4,6-Diarylpyridin-2-yl)acetamides as Potent and Selective Antagonists

We report the first family of 2-acetamidopyridines as potent and selective A3 adenosine receptor (AR) antagonists. The computer-assisted design was focused on the bioisosteric replacement of the N1 atom by a CH group in a previous series of diarylpyrimidines. Some of the generated 2-acetamidopyridines elicit an antagonistic effect with excellent affinity (Ki 3AR, and exemplifies the benefits of a joint theoretical–experimental approach to identify novel hA3AR antagonists through succinct and efficient synthetic methodologies.