有机化学 ›› 2015, Vol. 35 ›› Issue (1): 191-199.DOI: 10.6023/cjoc201405032 上一篇    下一篇

研究论文

3,5,6-三取代-1,2,4-三嗪衍生物合成、表征及生物活性

李英俊a, 史相玲a, 高立信b, 靳焜c, 盛丽b, 吴疆红a, 彭立娜a, 李佳b   

  1. a 辽宁师范大学化学化工学院 大连 116029;
    b 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;
    c 大连理工大学精细化工国家重点实验室 大连 116012
  • 收稿日期:2014-05-21 修回日期:2014-07-25 出版日期:2015-01-25 发布日期:2014-09-09
  • 通讯作者: 李英俊, 李佳 E-mail:chemlab.lnnu@163.com

Synthesis, Characterization and Biological Activities of 3,5,6-Trisubstituted-1,2,4-triazine Derivatives

Li Yingjuna, Shi Xianglinga, Gao Lixinb, Jin Kunc, Sheng Lib, Wu Jianghonga, Peng Linaa, Li Jiab   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
    c State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012
  • Received:2014-05-21 Revised:2014-07-25 Online:2015-01-25 Published:2014-09-09

在NH4OAc/HOAc存在下, 利用微波辅助, 将联苯甲酰/茴香偶酰与2-芳氧甲基苯并咪唑-1-乙酰肼(3)缩合, 合成出了30个新的含苯并咪唑环的3,5,6-三取代-1,2,4-三嗪衍生物56. 利用元素分析, IR, 1H NMR及单晶X射线衍射进行了结构表征. 评价了目标化合物对Cdc25B和PTP1B的抑制活性, 讨论了结构与活性的关系. 实验结果表明, 部分目标化合物对Cdc25B和PTP1B具有良好的抑制活性, 其中6o对Cdc25B的抑制活性[IC50=(0.84±0.22) μg/mL]最高. 目标化合物5i, 5m, 5n, 6h, 6j, 6m, 6n6o对PTP1B的抑制活性[IC50=(0.46±0.10)~(0.87±0.19) μg/mL] 均高于阳性对照药物齐墩果酸[IC50=(0.97±0.15) μg/mL]. 值得注意的是, 化合物5h, 5m, 6n6o对Cdc25B和PTP1B均具有抑制活性. 目标化合物是潜在的Cdc25B和PTP1B抑制剂.

关键词: 3,5,6-三取代-1,2,4-三嗪, 苯并咪唑, 微波辐射, 合成, 晶体结构, Cdc25B和 PTP1B抑制剂

Thirty new 3,5,6-trisubstituted-1,2,4-triazine derivatives containing benzimidazole moiety (56) were synthesized via microwave-assisted condensation reactions of 2-aryloxymethylbenzimidazole-1-acetylhydrazines (3) with benzil/p-anisil in the presence of NH4OAc/HOAc. The structures were characterized by elemental analysis, IR, 1H NMR spectra and single crystal X-ray determination. The synthesized target compounds were evaluated for Cdc25B and PTP1B inhibitory activities. The structure-activity relationship (SAR) was also briefly discussed. The experimental results indicated that some compounds showed good inhibitory activities against Cdc25B and PTP1B. Among of them, compound 6o [IC50=(0.84±0.22) μg/mL] exhibited highest inhibitory activity against Cdc25B. Compounds 5i, 5m, 5n, 6h, 6j, 6m, 6n and 6o showed higher inhibitory activities against PTP1B [IC50=(0.46±0.10)~(0.87±0.19) μg/mL] than positive control oleanolic acid [IC50=(0.97±0.15) μg/mL]. It is noteworthy that, compounds 5h, 5m, 6n and 6o showed inhibitory activities against Cdc25B and PTP1B. The target compounds can be considered as potential Cdc25B and PTP1B inhibitors.

Key words: 3,5,6-trisubstituted-1,2,4-triazine, benzimidazole, microwave irradiation, synthesis, crystal structure, Cdc25B and PTP1B inhibitors