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

…, L Boulet, C Brideau, A Chau, D Claveau…

Index: Giroux, Andre; Boulet, Louise; Brideau, Christine; Chau, Anh; Claveau, David; Cote, Bernard; Ethier, Diane; Frenette, Richard; Gagnon, Marc; Guay, Jocelyne; Guiral, Sebastien; Mancini, Joseph; Martins, Evelyn; Masse, Frederic; Methot, Nathalie; Riendeau, Denis; Rubin, Joel; Xu, Daigen; Yu, Hongping; Ducharme, Yves; Friesen, Richard W. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 20 p. 5837 - 5841

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Citation Number: 45

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 μM, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14mg/kg. Both active and selective ...