高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (7): 1445-1450.doi: 10.7503/cjcu20131194

• 有机化学 • 上一篇    下一篇

1,4-双[3-脂肪基/苯基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑-6-基]芳基衍生物的合成与生物活性

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

  1. 辽宁省生物与制药重点实验室, 辽宁师范大学化学化工学院, 大连 116029
  • 收稿日期:2013-12-06 出版日期:2014-07-10 发布日期:2014-04-21
  • 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项目(批准号: 2009A426)资助

Synthesis and Bioactivity of 1,4-Bis[3-aliphatic/aryl -1,2,4-triazole[3,4-b]-1,3,4-thiatriazole-6-yl] Aryl Derivatives

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

  1. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, China
  • Received:2013-12-06 Online:2014-07-10 Published:2014-04-21
  • Contact: ZHANG Chenglu E-mail:zhangchenglu@lnnu.edu.cn
  • Supported by:
    Supported by the Science and Technology Research Program of Liaoning Provincial Department of Education, China(No.2009A426).

摘要:

在三氯氧磷催化下, 6种3-脂肪基-1,2,4-三唑(1a~1f)和3-苯基-1,2,4-三唑(1g)分别与对苯二甲酸和2-氨基-1,4-对苯二甲酸发生环化反应, 高产率合成了14种双枝三唑并噻二唑稠环衍生物(2和3), 并对其进行了结构表征及药物活性测试. 目标化合物对Cdc25B和PTP1B抑制活性筛选结果表明, 化合物2f, 3a和3g对Cdc25B有较高的抑制活性, IC50值分别为(3.45±0.60), (0.69±0.10)和(1.52±0.19) μg/mL; 化合物3a和3b对PTP1B表现出较高的抑制活性, IC50值分别为(0.98±0.13)和(2.00±0.16) μg/mL.

关键词: 3-脂肪基-1, 2, 4-三唑并噻二唑, Cdc25B, PTP1B

Abstract:

Fourteen new bis-1,2,4-triazole[3,4-b]-[1,3,4]thiadiazol-6-yl derivatives(2 and 3) were synthesized in high yields through the reactions of six 3-aliphatic-1,2,4-triazole derivatives(1a—1f) and 3-phe-nyl-1,2,4-triazole(1g) with terephthalic acid and 2-aminoterephthalic acid, respectively, in the presence of phosphorus oxychloride. The structures of target compounds were characterized and the inhibitory properties of Cdc25B and PTP1B were studied. The results showed that compounds 2f, 3a and 3g exhibited high inhibitory activity against Cdc25B enzyme with IC50 values of (3.45±0.60), (0.69±0.10) and (1.52±0.19) μg/mL, respectively. Compounds 3a and 3b showed high inhibitory activity against PTP1B with IC50 values of (0.98±0.13) and (2.00±0.16) μg/mL.

Key words: 3-Aliphatic-1, 2, 4-triazole [3, 4-b]-1, 3, 4-thiatriazole, Cell division cycle 25B(Cdc25B), Protein tyrosine phosphatases 1B(PTP1B)

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