RSK2激酶小分子抑制剂的设计、合成和构效关系分析

doi:10.5246/jcps.2012.05.053

RSK2激酶小分子抑制剂的设计、合成和构效关系分析

薛梦竹, 袁俊, 吴彬, 赵雪, 刘晓峰, 黄瑾, 赵振江^*, 李洪林^*, 徐玉芳

1. 华东理工大学药学院上海市新药设计重点实验室, 上海 200237
2. 华东理工大学药学院上海市化学生物学重点实验室, 上海 200237

收稿日期:2012-06-12 修回日期:2012-07-25 出版日期:2012-09-15 发布日期:2012-09-15
通讯作者: 赵振江*, 李洪林*

Novel inhibitors for p90 ribosomal S6 protein kinase 2: design, synthesis and SAR

Mengzhu Xue, Jun Yuan, Bin Wu, Xue Zhao, Xiaofeng Liu, Jin Huang, Zhenjiang Zhao^*, Honglin Li^*, Yufang Xu

1. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
2. Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

Received:2012-06-12 Revised:2012-07-25 Online:2012-09-15 Published:2012-09-15
Contact: Zhenjiang Zhao*, Honglin Li*

摘要/Abstract

摘要：

通过对基于配体的虚拟筛选方法获得的先导化合物的结构优化, 设计、合成了一系列苯甲酰肼衍生物, 通过¹H NMR、¹³C NMR和MS确定了化合物结构。生物活性测试表明, 该系列化合物对RSK2激酶有中等程度的抑制作用。初步揭示了抑制RSK2活性的构效关系, 并通过模建的RSK2氮端三维结构揭示了该系列化合物抑制RSK2的作用机制。

关键词: RSK2激酶抑制剂, 苯甲酰肼衍生物, 构效关系, 分子对接

Abstract:

A series of benzohydrazide derivatives as novel ribosomal S6 kinase 2 (RSK2) inhibitors were designed and synthesized from a hit compound previously discovered by ligand-based virtual screening. Biological assays showed that these compounds possessed moderate inhibitory activities towards RSK2. The structural activity relationships (SAR) were elucidated by molecular docking and further optimization was performed.

Key words: RSK2 inhibitors, Benzohydrazide derivatives, SAR, Molecular docking

中图分类号:

R916

Supporting: Foundation items: The Fundamental Research Funds for the Central Universities, the National Natural Science Foundation of China (Grants No. 21173076, 81102375 and 81102420), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grants No. 20090074120012 and 20110074120009), the Shanghai Committee of Science and Technology (Grants No. 11DZ2260600 and 10431902600), the Innovation Program of Shanghai Municipal Education Commission (Grant No. 10ZZ41), and the 863 Hi-Tech Program of China (Grant No. 2012AA020308).
^*Corresponding author. Tel.: 86-21-64253962

薛梦竹, 袁俊, 吴彬, 赵雪, 刘晓峰, 黄瑾, 赵振江^*, 李洪林^*, 徐玉芳. RSK2激酶小分子抑制剂的设计、合成和构效关系分析[J]. , DOI: 10.5246/jcps.2012.05.053.

Mengzhu Xue, Jun Yuan, Bin Wu, Xue Zhao, Xiaofeng Liu, Jin Huang, Zhenjiang Zhao^*, Honglin Li^*, Yufang Xu. Novel inhibitors for p90 ribosomal S6 protein kinase 2: design, synthesis and SAR[J]. , DOI: 10.5246/jcps.2012.05.053.

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