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

Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6816-20. doi: 10.1016/j.bmcl.2007.10.033.
Bernard Côté 1,  Louise Boulet,  Christine Brideau,  David Claveau,  Diane Ethier,  Richard Frenette,  Marc Gagnon,  André Giroux,  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. [email protected]
PMID: 18029174 DOI: 10.1016/j.bmcl.2007.10.033
Abstract

Phenanthrene imidazole 3 (MF63) has been identified as a novel potent, selective, and orally active mPGES-1 inhibitor. This new series was developed by lead optimization of a hit from an internal HTS campaign. Compound 3 is significantly more potent than the previously reported indole carboxylic acid 1 with an A549 whole cell IC(50) of 0.42 microM (50% FBS) and a human whole blood IC(50) of 1.3 microM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100mg/kg.

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