2. Academic Validation
  3. Naphthalene/quinoline amides and sulfonylureas as potent and selective antagonists of the EP4 receptor

Naphthalene/quinoline amides and sulfonylureas as potent and selective antagonists of the EP4 receptor

  • Bioorg Med Chem Lett. 2011 Feb 1;21(3):1041-6. doi: 10.1016/j.bmcl.2010.12.014.
Jason D Burch 1,  Julie Farand,  John Colucci,  Claudio Sturino,  Yves Ducharme,  Richard W Friesen,  Jean-François Lévesque,  Sébastien Gagné,  Mark Wrona,  Alex G Therien,  Marie-Claude Mathieu,  Danielle Denis,  Erika Vigneault,  Daigen Xu,  Patsy Clark,  Steve Rowland,  Yongxin Han
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd, 16711 Trans-Canada Hwy. Kirkland, Québec, Canada H9H 3L1.
PMID: 21215624 DOI: 10.1016/j.bmcl.2010.12.014
Abstract

Two new series of EP(4) antagonists based on naphthalene/quinoline scaffolds have been identified as part of our on-going efforts to develop treatments for inflammatory pain. One series contains an acidic sulfonylurea pharmacophore, whereas the Other is a neutral amide. Both series show subnanomolar intrinsic binding potency towards the EP(4) receptor, and excellent selectivity towards Other prostanoid receptors. While the amide series generally displays poor pharmacokinetic parameters, the sulfonylureas exhibit greatly improved profile. MF-592, the optimal compound from the sulfonylurea series, has a desirable overall preclinical profile that suggests it is suitable for further development.

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