Novel 3-oxazolidinedione-6-aryl-pyridinones as potent, selective, and orally active EP3 receptor antagonists

…, Á Morales-Ramos, P Eidam, J Mecom…

Index: Jin, Jian; Morales-Ramos, Angel; Eidam, Patrick; Mecom, John; Li, Yue; Brooks, Carl; Hilfiker, Mark; Zhang, David; Wang, Ning; Shi, Dongchuan; Tseng, Pei-San; Wheless, Karen; Budzik, Brian; Evans, Karen; Jaworski, Jon-Paul; Jugus, Jack; Leon, Lisa; Wu, Charlene; Pullen, Mark; Karamshi, Bhumika; Rao, Parvathi; Ward, Emma; Laping, Nicholas; Evans, Christopher; Leach, Colin; Holt, Dennis; Su, Xin; Morrow, Dwight; Fries, Harvey; Thorneloe, Kevin; Edwards, Richard ACS Medicinal Chemistry Letters, 2010 , vol. 1, # 7 p. 316 - 320

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Citation Number: 6

Abstract

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 ...