Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S: Effect of sulfonamides P3 substituents on potency and selectivity
Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S: Effect of sulfonamides P3 substituents on potency and selectivity
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DOI：
10.1016/j.bmc.2008.12.020
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Samuelsson, Bertil
中科院分区：
文献类型：
--
作者：
Ayesa, Susana;Lindquist, Charlotta;Samuelsson, Bertil
描述了组织蛋白酶S的高效和选择性的4-氨基呋喃-3-酮抑制剂。介绍了一系列P3位含磺酰胺基的抑制剂的合成及构效关系。该系列的几个成员显示出对靶酶的亚纳摩尔抑制以及优异的选择性亲。le和良好的细胞效能。最有趣的抑制剂的分子建模描述了扩展的S3口袋中的相互作用，并解释了观察到的对组织蛋白酶K的选择性。(c)2008爱思唯尔有限公司保留所有权利。
Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure-activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity pro. le and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K. (c) 2008 Elsevier Ltd. All rights reserved.