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ID: ALA1681669

Journal: Bioorg Med Chem Lett

Title: Trisubstituted ureas as potent and selective mPGES-1 inhibitors.

Authors: Chiasson JF, Boulet L, Brideau C, Chau A, Claveau D, Côté B, Ethier D, Giroux A, Guay J, Guiral S, Mancini J, Massé F, Méthot N, Riendeau D, Roy P, Rubin J, Xu D, Yu H, Ducharme Y, Friesen RW.

Abstract: A novel series of trisubstituted ureas has been identified as potent and selective mPGES-1 inhibitors. These compounds are selective over other prostanoid enzymes such as PGF synthase and TX synthase. This series of inhibitors was developed by lead optimization of a hit from an internal HTS campaign. Lead compound 42 is potent in A549 cell assay (IC(50) of 0.34 μM) and in human whole blood assay (IC(50) of 2.1 μM). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors.

CiteXplore: 21295979

DOI: 10.1016/j.bmcl.2011.01.006