Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors

被引：31

作者：

Cheng, Xian-Chao ^{[1
]}

Wang, Qiang ^{[1
]}

Fang, Hao ^{[1
]}

Tang, Wei ^{[2
]}

Xu, Wen-Fang ^{[1
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Inst Med Chem, Jinan 250012, Peoples R China

[2] Univ Tokyo, Grad Sch Med, Dept Surg, Hepato Biliary Pancreat Surg Div, Tokyo 1138655, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 17期

基金：

国家高技术研究发展计划(863计划);

关键词：

pyrrolidine derivatives; synthesis; MMP-2; inhibitors; IC50;

D O I：

10.1016/j.bmc.2008.07.073

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of new sulfonyl pyrrolidine derivatives was designed, synthesized, and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than the positive control LY52. The FlexX docking was done to explain the reason for the different potency between MMP-2 and AP-N. Structure-activity relationships were also briefly discussed. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7932 / 7938

页数：7

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