Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 15, Issue 5, Pages 1529-1534Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2004.12.088
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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. (c) 2005 Elsevier Ltd. All rights reserved.
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