Novel 1,2,4-oxadiazoles and trifluoromethylpyridines related to natural products: synthesis, structural analysis and investigation of their antitumor activity
Novel 1,2,4-oxadiazoles and trifluoromethylpyridines related to natural products: synthesis, structural analysis and investigation of their antitumor activity
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DOI：
10.1016/j.tet.2016.01.011
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发表时间：
2016-03-03
期刊：
影响因子：
2.1
通讯作者：
Neda, Ion
中科院分区：
文献类型：
--
作者：
Maftei, Catalin V.;Fodor, Elena;Neda, Ion
介绍了新型1，2，4-恶二唑和三氟甲基吡啶衍生物的设计、结构表征及其潜在的医药应用。从两种容易获得的化合物开始，4-（3-（叔丁基）-1，2，4-恶二唑-5-基）苯胺（1）和2-（3-氯-5-（三氟甲基）吡啶-2-基）乙胺（10），掺入其它生物活性部分（如吡唑、吡唑并[3，4-d]嘧啶），以改变分子的亲脂性，从而可以改善生物活性单元通过细胞壁屏障的转运。通过在一组12个细胞系中的单层增殖测定来评估这些化合物的体外抗癌活性。发现17具有良好的效力，其表现出5.66 μ M的平均IC 50值，而其它化合物表现出较小的活性或没有活性。化合物3，5，7-9，11，12和17的固态结构通过X-射线衍射分析确定。(C)2016爱思唯尔有限公司版权所有
The design, structural characterization and potential medical application of novel 1,2,4-oxadiazole and trifluoromethylpyridine derivatives are described. Starting from two readily available compounds, 4-(3-(tert-butyl)-1,2,4-oxadiazol-5-yl)aniline (1) and 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethanamine (10), other bioactive moieties were incorporated (such as pyrazole, pyrazolo[3,4-d]pyrimidine), in order to modify the lipophilicity of the molecules, so that the transport of the bioactive units though the cell wall barrier could be improved. In vitro anti-cancer activity of these compounds was assessed by a monolayer proliferation assay in a panel of 12 cell lines. A good potency was found for 17, which exhibited a mean IC50 value of 5.66 mu M, while the other compounds exhibit minor or no activity. The solid state structures of compounds 3, 5, 7-9, 11, 12 and 17 were established by X-ray diffraction analyses. (C) 2016 Elsevier Ltd. All rights reserved.