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ID: ALA1141905

Journal: Bioorg Med Chem Lett

Title: 3,4-disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P3 elements for potency and selectivity.

Authors: Setti EL, Davis D, Janc JW, Jeffery DA, Cheung H, Yu W.

Abstract: The synthesis of a series of highly potent and selective inhibitors of cathepsin K based on the 3,4-disubstituted azetidin-2-one warhead is reported. A high degree of potency and selectivity was achieved by introducing a basic nitrogen into the distal part of the P3 element of the molecule. Data from kinetic and mass spectrometry experiments are consistent with the interpretation that compounds of this series transiently acylate the sulfhydrile of cathepsin K.

CiteXplore: 15713422

DOI: 10.1016/j.bmcl.2004.12.088