高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (3): 463.doi: 10.7503/cjcu20140918

• 有机化学 • 上一篇    下一篇

V型对称三唑并噻二唑衍生物的合成与生物活性

张成路(), 王雪, 胡雪, 孙丽杰, 曲瑞峰, 国阳, 柴金华, 朱长安   

  1. 辽宁师范大学化学化工学院, 辽宁省生物与制药重点实验室, 大连 116029
  • 收稿日期:2014-10-14 出版日期:2015-03-10 发布日期:2015-01-30
  • 作者简介:联系人简介: 张成路, 男, 博士, 教授, 主要从事有机合成研究. E-mail: zhangchenglu@lnnu.edu.cn
  • 基金资助:
    辽宁省教育厅科学技术资助项目(批准号: 2009A426)资助

Syntheses and Biological Activities of V-Shaped Symmetrical Triazolothiazine Oxadiazole Derivatives

ZHANG Chenglu*(), WANG Xue, HU Xue, SUN Lijie, QU Ruifeng, GUO Yang, CHAI Jinhua, ZHU Chang’an   

  1. College of Chemistry and Chemical Engineering, Liaoning Provincial key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029, China
  • Received:2014-10-14 Online:2015-03-10 Published:2015-01-30
  • Contact: ZHANG Chenglu E-mail:zhangchenglu@lnnu.edu.cn

摘要:

为构筑V型对称结构的三唑并噻二唑类衍生物, 将间苯二甲酸和5-氨基间苯二甲酸分别与3-脂肪基-1,2,4-三唑(1)缩合, 在POCl3催化下, 合成了14个V型对称结构三唑并噻二唑稠环衍生物(2a~2g和3a~3g), 其中13个化合物为首次合成.通过红外光谱、 核磁共振波谱和高分辨质谱等对目标产物的结构进行了表征. 研究了目标产物对细胞周期分裂蛋白25B(Cdc25B)和蛋白酪氨酸磷酸酶1B(PTP1B)的抑制性能, 结果发现, 部分目标产物对Cdc25B表现出良好的抑制活性, 其中化合物3b和3f的抑制活性IC50值分别为(1.34±0.39)和(0.61±0.09) μg/mL, 有望作为治疗癌症的潜在Cdc25B抑制剂; 化合物3b~3g对PTP1B均表现出良好的抑制活性, 其中化合物3b和3e的IC50值分别为(0.36±0.05)和(0.97±0.08) μg/mL, 有望作为治糖尿病的潜在PTP1B抑制剂.

关键词: 3-脂肪基-1,2,4-三唑, 药物活性筛选, Cdc25B, PTP1B

Abstract:

To build V-shaped symmetrical structure thiadiazole derivatives, isophthalic acid and 5-aminoisophthalic acid condensed with 3-aliphatic-1,2,4-triazole(1) respectively. In POCl3 presence, fourteen symmetrical V-shaped triazolo-thiadiazole derivatives(2a—2g and 3a—3g) were synthesized, wherein thirteen of them were first synthesized, and the structures of compounds 2 and 3 were characterized by infrared(IR), nuclear magnetic resonance(NMR) and high resolution mass spectrometer(HRMS). The inhibitory activities of the target compounds were screened for Cdc25B and PTP1B. The results showed that some compouds exhibited inhibitory activities against Cdc25B, compounds 3b and 3f may be used as potential Cdc25B inhibitors in the treatment of cancer. Compouds 3b—3g exhibited inhibitory activities against PTP1B. Compounds 3b and 3e may be used as potential PTP1B inhibitors in the treatment of diabetes.

Key words: 3-Aliphatic triazole, Drug activity screening, Cell devision cycle B(Cdc25B), Protein tyrosine phosphatase 1B(PTP1B)

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