Discovery of substituted-2,4-dimethyl-(naphthalene-4-carbonyl)amino-benzoic acid as potent and selective EP4 antagonists

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):105-9. doi: 10.1016/j.bmcl.2015.11.023.
Maria-Jesus Blanco  1 ,  Tatiana Vetman  2 ,  Srinivasan Chandrasekhar  2 ,  Matthew J Fisher  2 ,  Anita Harvey  2 ,  Daniel Mudra  2 ,  Xu-Shan Wang  2 ,  Xiao-Peng Yu  2 ,  Matthew A Schiffler  2 ,  Alan M Warshawsky  2
Affiliations
  • 1. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States. Electronic address: [email protected].
  • 2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
PMID: 26608552 DOI: 10.1016/j.bmcl.2015.11.023
Abstract

A novel series of EP4 antagonists, based on a quinoline scaffold, has been discovered. Medicinal chemistry efforts to optimize the potency of the initial hit are described. A highly potent compound in a clinically relevant human whole blood assay was identified. Selectivity and pharmacokinetic profiles of this compound are discussed.

Keywords
Arthritis pain; EP4 receptor antagonist; Human whole blood assay; Prostaglandin E2.