Ontology highlight
ABSTRACT:
SUBMITTER: Hu E
PROVIDER: S-EPMC4060924 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Hu Essa E Andrews Kristin K Chmait Samer S Zhao Xiaoning X Davis Carl C Miller Silke S Hill Della Puppa Geraldine G Dovlatyan Mary M Chen Hang H Lester-Zeiner Dianna D Able Jessica J Biorn Christopher C Ma Ji J Shi Jianxia J Treanor James J Allen Jennifer R JR
ACS medicinal chemistry letters 20140328 6
We report the discovery of novel imidazo[4,5-b]pyridines as potent and selective inhibitors of PDE10A. The investigation began with our recently disclosed ketobenzimidazole 1, which exhibited single digit nanomolar PDE10A activity but poor oral bioavailability. To improve oral bioavailability, we turned to novel scaffold imidazo[4,5-b]pyridine 2, which not only retained nanomolar PDE10A activity but was also devoid of the morpholine metabolic liability. Structure-activity relationship studies we ...[more]