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Bioorg Med Chem Lett. 2009 Oct 15;19(20):5837-41. doi: 10.1016/j.bmcl.2009.08.085. Epub 2009 Aug 28.

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

Author information

1
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que., Canada H9H 3L1. andre_giroux@merck.com

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.

PMID:
19748780
DOI:
10.1016/j.bmcl.2009.08.085
[Indexed for MEDLINE]

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