Discovery and characterization of a potent and selective EP4 receptor antagonist

  • Bioorg Med Chem Lett. 2015 Aug 15;25(16):3176-8. doi: 10.1016/j.bmcl.2015.05.091.
Matthew A Schiffler  1 ,  Srinivasan Chandrasekhar  2 ,  Matthew J Fisher  2 ,  Anita Harvey  2 ,  Steven L Kuklish  2 ,  Xu-Shan Wang  2 ,  Alan M Warshawsky  2 ,  Jeremy S York  2 ,  Xiao-Peng Yu  2
Affiliations
  • 1. Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285 USA. Electronic address: [email protected].
  • 2. Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, IN 46285 USA.
PMID: 26091726 DOI: 10.1016/j.bmcl.2015.05.091
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.

Keywords
Amphoteric; Dog bioavailability; EP(4) antagonist; Prostaglandin pathway.