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: schifflerma@lilly.com.
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.

Name
Email *

	Sorry, but the email address you supplied was invalid.