1,3-硒唑为模板多种杂环修饰的新型分子的设计、合成及活性研究

doi:10.6023/cjoc201607024

有机化学 ›› 2017, Vol. 37 ›› Issue (2): 440-454.DOI: 10.6023/cjoc201607024 上一篇下一篇

研究论文

1,3-硒唑为模板多种杂环修饰的新型分子的设计、合成及活性研究

张成路, 孙晓娜, 蒲雨昕, 李传银, 孙丽杰, 王静, 李益政

辽宁师范大学化学化工学院大连 116029

收稿日期:2016-07-15 修回日期:2016-09-03 发布日期:2016-10-09
通讯作者: 张成路 E-mail:zhangchenglu@lnnu.edu.cn
基金资助:
辽宁省教育厅科学技术研究（No.2009A426）资助项目.

Design, Synthesis and Activities of Multiheterocyclic Modified Novel Molecules Using 1,3-Selenazole as Template

Zhang Chenglu, Sun Xiaona, Pu Yuxin, Li Chuanyin, Sun Lijie, Wang Jing, Li Yizheng

College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029

Received:2016-07-15 Revised:2016-09-03 Published:2016-10-09
Supported by:
Project supported by the Science and Technology Research Program of Liaoning Provincial Department of Education (No. 2009A426).

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1. 1,3-硒唑为模板多种杂环修饰的新型分子的设计、合成及活性研究.PDF(12248KB)

摘要/Abstract

以取代1，3-硒唑为模板，分别利用1，2，4-三唑、四唑、噁二唑、吡唑、1，2，4-三嗪和丁二酰亚胺等修饰，首次设计合成了6类共22个目标分子，并利用IR，NMR和HRMS等波谱技术对目标分子进行了结构表征.评价了目标分子对Cdc25B的抑制活性，结果发现，13个目标分子具有较好的抑制活性，其中有5种目标分子的抑制活性高于阳性参照物Na₃VO₄有望成为抗肿瘤药物先导物.构效分析结果发现，在1，3-硒唑骨架上引入多氮杂环三唑、四唑和三嗪，引入含有氨基和巯基的噻二唑和噁二唑等有望获得活性优良的新型含硒有机分子

关键词: 1,3-硒唑, 多杂环, Cdc25B抑制剂

Six kinds, twenty-two novel target molecules were first designed and synthesized by using substituted 1,3-selenazole as a template, which were modified by 1,2,4-triazole, tetrazole, oxadiazole, pyrazole, 1,2,4-triazine and succinic imide respectively. Their structures were confirmed by IR, NMR and HRMS. The inhibitory activities of the target molecules against cell division cycle 25B phosphatase (Cdc25B) were evaluated. As a result, thirteen compounds exhibited good inhibitory activities. The IC₅₀ values of five compounds were lower than the positive reference Na₃VO₄ and were expected to be anticancer drugs leading compounds. The analysis of structure-activity relationship found that the introduction of multinitrgon-heterocyclic triazole, tetrazole and triazine, thiadiazole and oxadiazole containing amino or mercapto group onto 1,3-selenazole were expected to obtain novel excellent bioactivity organic selenium containing molecules.

Key words: 1,3-selenazole, multi-heterocycle, Cdc25B inhibitor

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张成路, 孙晓娜, 蒲雨昕, 李传银, 孙丽杰, 王静, 李益政. 1,3-硒唑为模板多种杂环修饰的新型分子的设计、合成及活性研究[J]. 有机化学, 2017, 37(2): 440-454.

Zhang Chenglu, Sun Xiaona, Pu Yuxin, Li Chuanyin, Sun Lijie, Wang Jing, Li Yizheng. Design, Synthesis and Activities of Multiheterocyclic Modified Novel Molecules Using 1,3-Selenazole as Template[J]. Chin. J. Org. Chem., 2017, 37(2): 440-454.

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1,3-硒唑为模板多种杂环修饰的新型分子的设计、合成及活性研究

Design, Synthesis and Activities of Multiheterocyclic Modified Novel Molecules Using 1,3-Selenazole as Template

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