2. Academic Validation
  3. Discovery of potent aryl-substituted 3-[(3-methylpyridine-2-carbonyl) amino]-2,4-dimethyl-benzoic acid EP4 antagonists with improved pharmacokinetic profile

Discovery of potent aryl-substituted 3-[(3-methylpyridine-2-carbonyl) amino]-2,4-dimethyl-benzoic acid EP4 antagonists with improved pharmacokinetic profile

  • Bioorg Med Chem Lett. 2016 Feb 1;26(3):931-935. doi: 10.1016/j.bmcl.2015.12.057.
Maria-Jesus Blanco 1,  Tatiana Vetman 2,  Srinivasan Chandrasekhar 2,  Matthew J Fisher 2,  Anita Harvey 2,  Mark Chambers 2,  Chaohua Lin 2,  Daniel Mudra 2,  Jennifer Oskins 2,  Xu-Shan Wang 2,  Xiao-Peng Yu 2,  Alan M Warshawsky 2
Affiliations

Affiliations

  • 1 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States. Electronic address: blanco_maria@lilly.com.
  • 2 Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, United States.
PMID: 26764191 DOI: 10.1016/j.bmcl.2015.12.057
Abstract

Two new series of EP4 antagonists containing a 3-methylaryl-2-carbonyl core have been identified. One series has a 3-substituted-phenyl core, while the Other one incorporates a 3-substituted pyridine. Both series led to compounds with potent activity in functional and human whole blood (hWB) assays. In the pyridine series, compound 7a was found to be a highly potent and selective EP4 antagonist, with suitable rat and dog pharmacokinetic profiles.

Keywords

EP4 receptor antagonist; Human whole blood (hWB) assay; Inflammation; Pain; Prostaglandin E2; Structure–activity relationship (SAR).

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