2. Academic Validation
  3. Trisubstituted ureas as potent and selective mPGES-1 inhibitors

Trisubstituted ureas as potent and selective mPGES-1 inhibitors

  • Bioorg Med Chem Lett. 2011 Mar 1;21(5):1488-92. doi: 10.1016/j.bmcl.2011.01.006.
Jean-François Chiasson 1,  Louise Boulet,  Christine Brideau,  Anh Chau,  David Claveau,  Bernard Côté,  Diane Ethier,  André Giroux,  Jocelyne Guay,  Sébastien Guiral,  Joseph Mancini,  Frédéric Massé,  Nathalie Méthot,  Denis Riendeau,  Patrick Roy,  Joel Rubin,  Daigen Xu,  Hongping Yu,  Yves Ducharme,  Richard W Friesen
Affiliations

Affiliation

  • 1 Merck Frosst Center for Therapeutic Research, Kirkland, Quebec, Canada. jfchiasson@gmail.com
PMID: 21295979 DOI: 10.1016/j.bmcl.2011.01.006
Abstract

A novel series of trisubstituted ureas has been identified as potent and selective mPGES-1 inhibitors. These compounds are selective over Other prostanoid Enzymes such as PGF synthase and TX synthase. This series of inhibitors was developed by lead optimization of a hit from an internal HTS campaign. Lead compound 42 is potent in A549 cell assay (IC(50) of 0.34 μM) and in human whole blood assay (IC(50) of 2.1 μM). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors.

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