Author/Authors :
Denis Riendeau، نويسنده , , Renée Aspiotis، نويسنده , , Diane Ethier، نويسنده , , Yves Gareau، نويسنده , , Erich L. Grimm، نويسنده , , Jocelyne Guay، نويسنده , , Sébastien Guiral، نويسنده , , Hélène Juteau، نويسنده , , Joseph A. Mancini، نويسنده , , Nathalie Méthot، نويسنده , , Joel Rubin، نويسنده , , Richard W. Friesen، نويسنده ,
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.
Keywords :
prostaglandin E2 , inflammation , Prostaglandin synthase , FLAP inhibitors , MK-886
