期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 11, 期 24, 页码 5449-5460出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2003.09.031
关键词
-
A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P-2 site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholinone was the most effective modification for inhibiting mu- and m-calpains. Substitutions of benzyl at the 5-position in the S-configuration had virtually no effect on inhibitory activity. Several compounds showed appreciable selectivity for calpains over cathepsin B. NMR experiments demonstrated that the representative 6-hydroxy-3-morpholinone 10a (SNJ-1757) was more stable to nucleophilic attack than the corresponding aldehyde inhibitor 24. Furthermore, 6-hydroxy-3-morpholinone 10a proved to have better corneal permeability than aldehyde inhibitor 24 in an in vitro experiment. (C) 2003 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据