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

doi:10.6023/cjoc201405032

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (1): 191-199.DOI: 10.6023/cjoc201405032 Previous Articles Next Articles

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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

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 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 Yingjun^a, Shi Xiangling^a, Gao Lixin^b, Jin Kun^c, Sheng Li^b, Wu Jianghong^a, Peng Lina^a, Li Jia^b

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 Published:2014-09-09

1. Synthesis, Characterization and Biological Activities of 3,5,6-Trisubstituted-1,2,4-triazine Derivatives.PDF(18282KB)

Abstract

Thirty new 3,5,6-trisubstituted-1,2,4-triazine derivatives containing benzimidazole moiety (5～6) 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

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Li Yingjun, Shi Xiangling, Gao Lixin, Jin Kun, Sheng Li, Wu Jianghong, Peng Lina, Li Jia. Synthesis, Characterization and Biological Activities of 3,5,6-Trisubstituted-1,2,4-triazine Derivatives[J]. Chin. J. Org. Chem., 2015, 35(1): 191-199.

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3,5,6-三取代-1,2,4-三嗪衍生物合成、表征及生物活性

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

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