Bioorg Med Chem Lett. 2005 Jul 15;15(14):3352-5.

Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886.

Riendeau D, Aspiotis R, Ethier D, Gareau Y, Grimm EL, Guay J, Guiral S, Juteau H, Mancini JA, Méthot N, Rubin J, Friesen RW.

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

Abstract

A series of potent and selective inhibitors of the inducible microsomal PGE2 synthase (mPGES-1) has been developed based on the indole FLAP inhibitor MK-886. Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and with selectivities of at least 100-fold compared to their inhibition of mPGES-2, thromboxane synthase and binding affinity to FLAP. They also block the production of PGE2 in cell based assays but with a decreased potency and more limited selectivity compared to the enzyme assays.

PMID:: 15953724; [PubMed - indexed for MEDLINE]

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Bioorg Med Chem Lett. 2005 Jul 15 ;15(14):3352-5.

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