Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors
2009; Elsevier BV; Volume: 19; Issue: 20 Linguagem: Inglês
10.1016/j.bmcl.2009.08.085
ISSN1464-3405
AutoresAndré Giroux, Louise Boulet, Christine Brideau, Anh Chau, David Claveau, Bernard Côté, Diane Ethier, Richard Frenette, Marc Gagnon, Jocelyne Guay, Sébastien Guiral, Joseph A. Mancini, Evelyn Martins, Frédéric Massé, Nathalie Méthot, Denis Riendeau, Joel Rubin, Daigen Xu, Hongping Yu, Yves Ducharme, Richard W. Friesen,
Tópico(s)Phytochemistry and Bioactive Compounds
ResumoPhenanthrene 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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