The discovery of 4-{1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic acid (MK-2894), a potent and selective prostaglandin E2 subtype 4 receptor antagonist

  • J Med Chem. 2010 Mar 11;53(5):2227-38. doi: 10.1021/jm901771h.
Marc Blouin  1 ,  Yongxin Han ,  Jason Burch ,  Julie Farand ,  Christophe Mellon ,  Mireille Gaudreault ,  Mark Wrona ,  Jean-François Lévesque ,  Danielle Denis ,  Marie-Claude Mathieu ,  Rino Stocco ,  Erika Vigneault ,  Alex Therien ,  Patsy Clark ,  Steve Rowland ,  Daigen Xu ,  Gary O'Neill ,  Yves Ducharme ,  Rick Friesen
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd., 16771 Trans-Canada Highway, Kirkland, QC, Canada. [email protected]
PMID: 20163116 DOI: 10.1021/jm901771h
Abstract

The discovery of highly potent and selective second generation EP(4) antagonist MK-2894 (34d) is discussed. This compound exhibits favorable pharmacokinetic profile in a number of preclinical species and potent anti-inflammatory activity in several animal models of Pain/inflammation. It also shows favorable GI tolerability profile in rats when compared to traditional NSAID indomethacin.

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