Ayesa Susana, Lindquist Charlotta, Agback Tatiana, Benkestock Kurt, Classon Björn, Henderson Ian, Hewitt Ellen, Jansson Katarina, Kallin Anders, Sheppard Dave, Samuelsson Bertil
Medivir AB, Lunastigen 7 SE-14144 Huddinge, Sweden.
Bioorg Med Chem. 2009 Feb 1;17(3):1307-24. doi: 10.1016/j.bmc.2008.12.020. Epub 2008 Dec 24.
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 profile 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.
描述了组织蛋白酶S的高效且选择性的4-氨基呋喃-3-酮抑制剂。介绍了一系列在P3位带有磺酰胺部分的抑制剂的合成及其构效关系。该系列中的几个成员对目标酶表现出亚纳摩尔级别的抑制作用，以及出色的选择性和良好的细胞活性。对最具吸引力的抑制剂进行分子建模，描述了其在扩展的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。
