Identification of novel adenosine A 2A receptor antagonists by virtual screening

Abstract

Virtual screening was performed against experimentally enabled homology models of the adenosine A 2A receptor, identifying a diverse range of ligand efficient antagonists (hit rate 9%). By use of ligand docking and Biophysical Mapping (BPM), hits 1 and 5 were optimized to potent and selective lead molecules (11-13 from 5, pK I = 7.5-8.5, 13- to >100-fold selective versus adenosine A 1; 14-16 from 1, pK I = 7.9-9.0, 19- to 59-fold selective). © 2012 American Chemical Society.