Fig. 2
Docking studies predicted molecular interactions similar to those observed for triazoloquinazolines in the A2AR protein crystal structure (PDB ID: 2YDO). Distinct binding modes are shown for compounds 1 and 4. a Compound 1 hydrogen bonds via the nitrogen of the quinazoline ring with Asn253 and via the imidazo ring with Glu169. The triazole ring is π-stacked with Phe168, and the phenyl group in quinazoline is π-stacked with His250 b Compound 4 shows π-stacking with Phe168. It can be seen that the A2AR selective agonist 1 is predicted to bind deeper within the binding site and interacts with His250 and Asn253, which is consistent with binding modes observed in crystallographic data (PDB IDs: 4UG2, 4UHR, 3QAK, 2YDO and 2YDV). The essential role of His250 in shaping the binding site was supported by MD simulation. Yellow spheres indicate lipophilic contacts, red arrows show hydrogen bond acceptors and purple disks indicate aromatic interactions