Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitors期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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

Authors:	Côté Bernard Boulet Louise Brideau Christine Claveau David Ethier Diane Frenette Richard Gagnon Marc Giroux André Guay Jocelyne Guiral Sébastien Mancini Joseph Martins Evelyn Massé Frédéric Méthot Nathalie Riendeau Denis Rubin Joel Xu Daigen Yu Hongping Ducharme Yves Friesen Richard W

Affiliation:	^aMerck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que., Canada H9H 3L1

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 IC₅₀ of 0.42 μM (50% FBS) and a human whole blood IC₅₀ of 1.3 μM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100 mg/kg.

Keywords:	mPGES-1 PGE₂ Inflammation Prostanoid
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