Fig. 1
The Structures of the identified PDE10A inhibitors with the potential to bind to the A2AR, and their pharmacology at PDE10A. a Virtual screening protocol. b Chemical structures for the six compounds identified in the in silico screen, literature references, compound IDs (used here) and pIC50 for PDE10A inhibition. c Concentration-response curves generated for 1–6 and CGS21680 at PDE10A. Data is the mean of six individual replicates ± SEM. d Representative binding modes proposed for the triazoloquinazolines 1 and 4 docked to the PDE10A crystal structure (PDB ID: 4DDL). Yellow spheres indicate lipophilic contacts. Aromatic interactions are illustrated by purple disks and hydrogen bond acceptors are shown as red arrows. Tyr683 is part of the “selectivity pocket” of PDE10A [33], and its interaction through a hydrogen bond with the thioether of both compounds could explain their subtype selectivity