有机化学 ›› 2014, Vol. 34 ›› Issue (2): 325-333.DOI: 10.6023/cjoc201309013 上一篇    下一篇

研究论文

新型咪唑[2,1-b][1,3,4]噻二唑衍生物的合成及Cdc25B抑制活性

李英俊a, 罗潼川a, 靳焜b, 高立信c, 邵昕a, 盛丽c, 于洋a, 李佳c   

  1. a 辽宁师范大学化学化工学院 大连 116029;
    b 大连理工大学精细化工国家重点实验室 大连 116012;
    c 中国科学院上海药物研究所国家新药筛选中心 药物研究国家重点实验室 上海 201203
  • 收稿日期:2013-09-06 修回日期:2013-10-28 出版日期:2014-02-25 发布日期:2013-11-05
  • 通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com
  • 基金资助:

    辽宁省自然科学基金(No.20102126)资助项目.

Synthesis and Cdc25B Inhibition Activity of Novel Imidazo[2,1-b][1,3,4]thiadiazole Derivatives

Li Yingjuna, Luo Tongchuana, Jin Kunb, Gao Lixinc, Shao Xina, Sheng Lic, Yu Yanga, Li Jiac   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012;
    c State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
  • Received:2013-09-06 Revised:2013-10-28 Online:2014-02-25 Published:2013-11-05
  • Supported by:

    Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

大量研究表明,细胞分裂周期25磷酸酯酶B(Cdc25B)在许多癌症中都是过度表达的,如乳腺癌、结肠癌、子宫颈癌、肺癌等. 因此,抑制Cdc25B是治疗癌症的一种潜在方法. 采用微波辐射法,合成出了20个新的2,6-二芳基-咪唑[2,1-b][1,3,4]噻二唑衍生物4,然后再经Vilsmeier-Haack反应,合成出了19个新的2,6-二芳基-咪唑[2,1-b][1,3,4]噻二 唑-5-甲醛(5). 利用IR,1H NMR和元素分析对新的中间体化合物3及目标产物45进行了结构表征. 对所合成的目标化合物45进行了Cdc25B抑制活性筛选. 实验结果表明,在浓度为5 μg/mL时,目标化合物4c对Cdc25B的抑制活性最高,抑制率为87.68%,目标化合物4o5m具有中等的抑制活性,其抑制率分别为55.76%和57.69%. 它们是潜在的Cdc25B抑制剂.

关键词: 咪唑[2,1-b][1,3,4]噻二唑, 微波, 合成, Cdc25B

Researches indicate that the cell division cycle 25 phosphatase B (Cdc25B) is over-expressed in various primary human cancers including breast, colon, cervix, lung, etc. This suggests that the inhibition of Cdc25B may become a promising strategy in oncology. In this work, twenty novel 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazoles 4 have been synthesized by microwave-assisted method. Then nineteen novel 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (5) have obtained by Vilsmeier-Haack reaction. The structures of new compounds 3, 4 and 5 were characterized by IR, 1H NMR spectra and elemental analysis. The synthesized target compounds 4 and 5 were screened for Cdc25B inhibitory activities. The results revealed that compound 4c showed the highest inhibitory activity against Cdc25B with percentage inhibition 87.68% at 5 μg/mL, compounds 4o and 5c showed moderate activities with percentage inhibition 55.76% and 57.69%, respectively. They can be considered as potential candidates as novel Cdc25B inhibitors.

Key words: imidazo[2,1-b][1,3,4]thiadiazole, microwave-assisted, synthesis, Cdc25B