Setti Eduardo L, Davis Dana, Janc James W, Jeffery Douglas A, Cheung Harry, Yu Walter
Celera Genomics, 180 Kimball Way, South San Francisco, CA 94080, USA.
Bioorg Med Chem Lett. 2005 Mar 1;15(5):1529-34. doi: 10.1016/j.bmcl.2004.12.088.
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.
报道了基于3,4-二取代氮杂环丁烷-2-酮弹头的一系列组织蛋白酶K的高效和选择性抑制剂的合成。通过将碱性氮引入分子P3元件的远端部分，实现了高度的效力和选择性。动力学和质谱实验数据与该系列化合物瞬时酰化组织蛋白酶K的巯基的解释一致。
