2. Academic Validation
  3. Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors

Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors

  • Bioorg Med Chem Lett. 2009 Oct 15;19(20):5837-41. doi: 10.1016/j.bmcl.2009.08.085.
André Giroux 1,  Louise Boulet,  Christine Brideau,  Anh Chau,  David Claveau,  Bernard Côté,  Diane Ethier,  Richard Frenette,  Marc Gagnon,  Jocelyne Guay,  Sébastien Guiral,  Joseph Mancini,  Evelyn Martins,  Frédéric Massé,  Nathalie Méthot,  Denis Riendeau,  Joel Rubin,  Daigen Xu,  Hongping Yu,  Yves Ducharme,  Richard W Friesen
Affiliations

Affiliation

  • 1 Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que., Canada H9H 3L1. [email protected]
PMID: 19748780 DOI: 10.1016/j.bmcl.2009.08.085
Abstract

Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC50 of 0.20 and 0.14 microM, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development.

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