Ontology highlight
ABSTRACT:
SUBMITTER: Jin J
PROVIDER: S-EPMC4007852 | biostudies-other | 2010 Oct
REPOSITORIES: biostudies-other
Jin Jian J Morales-Ramos Angel A Eidam Patrick P Mecom John J Li Yue Y Brooks Carl C Hilfiker Mark M Zhang David D Wang Ning N Shi Dongchuan D Tseng Pei-San PS Wheless Karen K Budzik Brian B Evans Karen K Jaworski Jon-Paul JP Jugus Jack J Leon Lisa L Wu Charlene C Pullen Mark M Karamshi Bhumika B Rao Parvathi P Ward Emma E Laping Nicholas N Evans Christopher C Leach Colin C Holt Dennis D Su Xin X Morrow Dwight D Fries Harvey H Thorneloe Kevin K Edwards Richard R
ACS medicinal chemistry letters 20100514 7
High-throughput screening and subsequent optimization led to the discovery of novel 3-oxazolidinedione-6-aryl-pyridinones exemplified by compound 2 as potent and selective EP3 antagonists with excellent pharmacokinetic properties. Compound 2 was orally active and showed robust in vivo activities in overactive bladder models. To address potential bioactivation liabilities of compound 2, further optimization resulted in compounds 9 and 10, which maintained excellent potency, selectivity, and pharm ...[more]