Bioorganic & Medicinal Chemistry Letters 2008-02-01

N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR.

Holly L Deak, John R Newcomb, Joseph J Nunes, Christina Boucher, Alan C Cheng, Erin F DiMauro, Linda F Epstein, Paul Gallant, Brian L Hodous, Xin Huang, Josie H Lee, Vinod F Patel, Stephen Schneider, Susan M Turci, Xiaotian Zhu

Index: Bioorg. Med. Chem. Lett. 18(3) , 1172-6, (2008)

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Abstract

N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.