Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors.

Abstract Novel triazoloquinazolines have been found as phosphodiesterase 10A (PDE10A) inhibitors. Structure–activity studies improved the initial micromolar potency which was found in the lead compound by a 100-fold identifying 5-(1 H -benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5- c ]quinazoline, 42 (PDE10A IC 50  = 12 nM) as the most potent compound from the series. Two X-ray structures revealed novel binding modes to the catalytic site of the PDE10A enzyme.