http://jcps.bjmu.edu.cn

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (10): 726-736.DOI: 10.5246/jcps.2016.10.081

• 【研究论文】 • 上一篇    下一篇

新型非ATP竞争型细胞周期检查点激酶1(CHK1)抑制剂的设计、合成及活性评估

李远新, 韩子飞, 田超*, 张志丽*, 刘俊义   

  1. 北京大学医学部 药学院 化学生物学系, 北京 100191
  • 收稿日期:2016-05-15 修回日期:2016-06-20 出版日期:2016-10-27 发布日期:2016-07-10
  • 通讯作者: Tel.: +86-010-82805203, E-mail: tianchao@bjmu.edu.cn
  • 基金资助:

    National Natural Science Foundation of China (Grant No. 21302007).

Design, synthesis and evaluation of novel non-ATP competitive CHK1 inhibitors as chemotherapy sensitizing agents

Yuanxin Li, Zifei Han, Chao Tian*, Zhili Zhang*, Junyi Liu   

  1. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2016-05-15 Revised:2016-06-20 Online:2016-10-27 Published:2016-07-10
  • Contact: Tel.: +86-010-82805203, E-mail: tianchao@bjmu.edu.cn
  • Supported by:

    National Natural Science Foundation of China (Grant No. 21302007).

摘要:

本文根据已报道的非ATP竞争型CHK1抑制剂, 设计并合成了分别具有吡咯并嘧啶和嘌呤结构的两类脲类化合物作为新型非ATP竞争型CHK1抑制剂, 并进行了初步的生物活性测试。结果显示, 大部分化合物尤其是嘌呤系列化合物17f 不仅对CHK1的抑制活性高于先导化合物, 而且展现出一定的抗肿瘤增强作用。

关键词: 细胞周期检查点激酶1, 非ATP竞争型抑制剂, 抗肿瘤协同作用

Abstract:

A series of urea-based compounds containing purine moieties were designed and synthesized as novel non-ATP competitive CHK1 inhibitors. The biological evaluation showed that several target compounds exhibited more potent inhibitory effects against CHK1 than the lead compound. In addition, one particular compound displayed synergistic effects with gemcitabine against HT29 cells.

Key words: CHK1 inhibitors, Non-ATP competitive, Anti-cancer synergistic effect

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