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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*   

  1. 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*

Abstract:

A novel series of pyrrolidinone analogs that are designed as Michael addition acceptors to react irreversibly with the proteasome active site Thr1Oγ 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

CLC Number: 

Supporting: