Discovery and characterization of a potent and selective EP4 receptor antagonist. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Schiffler, Matthew A.; Chandrasekhar, Srinivasan; Fisher, Matthew J.; Harvey, Anita; Kuklish, Steven L.; Wang, Xu-Shan; Warshawsky, Alan M.; York, Jeremy S.; Yu, Xiao-Peng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3176
• Page End: 3178
• Publication Date: 2015-08-15
• Subjects: CFA complete Freund's adjuvant -- CHO Chinese hamster ovary; EP4 antagonist -- Prostaglandin pathway -- Dog bioavailability -- Amphoteric; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.091
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: EP4 is a prostaglandin E2 receptor that is a target for potential anti-nociceptive therapy. Described herein is a class of amphoteric EP4 antagonists which reverses PGE2 -induced suppression of TNFα production in human whole blood. From this class, a potent and highly bioavailable compound (6 ) has been selected for potential clinical studies. EP4 binding and functional data, selectivity, and pharmacokinetic properties of this compound are included.