Inhibitors of the inducible microsomal prostaglandin E 2 synthase (mPGES-1) derived from MK-886

…, D Ethier, Y Gareau, EL Grimm, J Guay, S Guiral…

Index: Riendeau, Denis; Aspiotis, Renee; Ethier, Diane; Gareau, Yves; Grimm, Erich L.; Guay, Jocelyne; Guiral, Sebastien; Juteau, Helene; Mancini, Joseph A.; Methot, Nathalie; Rubin, Joel; Friesen, Richard W. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 14 p. 3352 - 3355

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Citation Number: 132

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 ...