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

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Kehler J, Ritzen A, Langgard M, Petersen SL, Farah MM, Bundgaard C, Christoffersen CT, Nielsen J, Kilburn JP

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

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3738-42. doi: 10.1016/j.bmcl.2011.04.067. Epub 2011 Apr 30.

PubMed ID
21602043 [ View in PubMed
]
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-(1H-benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5-c]quinazolin e, 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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MardepodectcAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AIC 50 (nM)2.6N/AN/ADetails
PapaverinecAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AIC 50 (nM)210N/AN/ADetails
PQ-10cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10AIC 50 (nM)64N/AN/ADetails