N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR

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.

Graphical abstractA novel class of selective Lck inhibitors is reported. X-ray co-crystal structural data, structure–activity relationships, and the synthesis of these inhibitors are described.Figure optionsDownload full-size imageDownload as PowerPoint slide