20S蛋白酶体抑制剂吡咯啉酮类似物的设计、合成及活性测试

doi:10.5246/jcps.2011.06.072

20S蛋白酶体抑制剂吡咯啉酮类似物的设计、合成及活性测试

李勇剑, 许凤荣, 牛彦, 邹晓民, 袁悦, 高海飞, 王超, 杨冠宇, 孙琦, 徐萍^*

北京大学医学部药学院药物化学系, 北京 100191

收稿日期:2011-05-24 修回日期:2011-09-02 出版日期:2011-11-15 发布日期:2011-11-15
通讯作者: 徐萍*

Design, synthesis and biological evaluation of pyrrolidinone analogs as potential 20S proteasome inhibitors

Yong-Jian Li, Feng-Rong Xu, Yan Niu, Xiao-Min Zou, Yue Yuan, Hai-Fei Gao, Chao Wang, Guan-Yu Yang, Qi Sun, Ping Xu^*

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-05-24 Revised:2011-09-02 Online:2011-11-15 Published:2011-11-15
Contact: Ping Xu*

摘要/Abstract

摘要： 本文设计并合成了一系列吡咯啉酮类似物, 这些化合物可能作为Michael受体与蛋白酶体活性位点Thr1O^γ不可逆结合, 从而抑制蛋白酶体的活性。虽然活性测试结果显示这些化合物对蛋白酶体的抑制活性很弱, 但是可以通过吡咯啉酮类化合物进一步的结构优化来提高对蛋白酶体的抑制活性。

关键词: 吡咯啉酮, 20S蛋白酶体, 拟肽骨架

Abstract:

A novel series of pyrrolidinone analogs that are designed as Michael addition acceptors to react irreversibly with the proteasome active site Thr1O^γ have been synthesized. Although biological evaluation results show that the compounds display poor inhibitory activity towards the proteasome active sites, pyrrolidinone analogs might still be modified to be potential 20S proteasome inhibitors.

Key words: Pyrrolidinone, 20S proteasome, Peptidomimetic backbone

中图分类号:

R916.1

Supporting:

Foundation item: Beijing Natural Science Foundation (Grant No. 7112088).
^*Corresponding author. Tel.: 86-10-82801505

李勇剑, 许凤荣, 牛彦, 邹晓民, 袁悦, 高海飞, 王超, 杨冠宇, 孙琦, 徐萍^*. 20S蛋白酶体抑制剂吡咯啉酮类似物的设计、合成及活性测试[J]. , DOI: 10.5246/jcps.2011.06.072.

Yong-Jian Li, Feng-Rong Xu, Yan Niu, Xiao-Min Zou, Yue Yuan, Hai-Fei Gao, Chao Wang, Guan-Yu Yang, Qi Sun, Ping Xu^* . Design, synthesis and biological evaluation of pyrrolidinone analogs as potential 20S proteasome inhibitors[J]. , DOI: 10.5246/jcps.2011.06.072.

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