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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Giroux A,Boulet L,Brideau C,Chau A,Claveau D,Côté B,Ethier D,Frenette R,Gagnon M,Guay J,Guiral S,Mancini J,Martins E,Massé F,Méthot N,Riendeau D,Rubin J,Xu D,Yu H,Ducharme Y,Friesen RW

doi

10.1016/j.bmcl.2009.08.085

subject

Has Abstract

pub_date

2009-10-15 00:00:00

pages

5837-41

issue

20

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01232-3

journal_volume

19

pub_type

杂志文章

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