Ontology highlight
ABSTRACT:
SUBMITTER: Ernst G
PROVIDER: S-EPMC7003998 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Ernst Glen G Akuma Daniel D Au Vinh V Buchler Ingrid P IP Byers Spencer S Carr Gregory V GV Defays Sabine S de León Pablo P Demaude Thierry T DePasquale Michael M Durieu Véronique V Huang Yifang Y Jigorel Emilie E Kimos Martha M Kolobova Anna A Montel Florian F Moureau Florence F Poslusney Michael M Swinnen Dominique D Vandergeten Marie-Christine MC Van Houtvin Nathalie N Wei Huijun H White Noelle N Wood Martyn M Barrow James C JC
ACS medicinal chemistry letters 20191022 11
A series of bicyclic pyridones were identified as potent inhibitors of catechol <i>O</i>-methyltransferase (COMT). Substituted benzyl groups attached to the basic nitrogen of the core scaffold gave the most potent inhibitors within this series. Rat pharmacokinetic studies showed medium to high levels of clearance for this series, but with high free fraction due to remarkably low levels of protein and tissue binding. In rat biomarker studies, levels of unbound drug exposure are seen in the brain, ...[more]