2,4,6-三取代嘧啶衍生物的合成及体外抗肿瘤活性研究
收稿日期: 2017-05-08
修回日期: 2017-05-23
网络出版日期: 2017-06-07
基金资助
国家自然科学基金（No.81430085）和郑州市科技局科研（No.141PQYJS554）资助项目.
Synthesis and Antitumor Activity Evaluation of 2,4,6-Trisubstituted Pyrimidine Derivatives
Received date: 2017-05-08
Revised date: 2017-05-23
Online published: 2017-06-07
Supported by
Project supported by the National Natural Science Foundation of China (No.81430085) and the Research Project of Science and Technology Bureau of Zhengzhou City (No.141PQYJS554).
为了寻找更高效、更经济的抗肿瘤药物，以乙酰乙酸乙酯和苯甲酰乙酸乙酯为起始原料，经环合、取代、氯代等反应合成了一系列具有查尔酮官能团的2，4，6-三取代嘧啶衍生物，共40个化合物.这些目标化合物的分子结构均经过1H NMR，13C NMR和HRMS确证，并利用CCK-8方法测试它们对MGC-803人胃癌细胞、HepG-2人肝癌细胞、EC-109人食管癌细胞和MDA-MB-231乳腺癌细胞四种人类癌细胞系的抗肿瘤活性研究.其中N-（3，4，5-三甲氧苯乙烯基苯基酮）-2-（苯并咪唑-2-亚甲硫基）-6-甲基嘧啶-4-胺（13u）对MGC-803和MDA-MB-231细胞株抗肿瘤活性要优于对照品5-氟尿嘧啶，其IC50值分别为0.99和1.77 μmol·L-1.
关键词： 2,4,6-三取代嘧啶; 查尔酮; 抗肿瘤
宋攀攀 , 栗娜 , 崔飞 , 辛景超 , 张孝松 , 曹钦坡 , 王超杰 , 戴文杰 , 孟祥川 , 刘梦 , 常通航 , 柳晴怡 , 孙月红 , 可钰 , 张秋荣 , 刘宏民 . 2,4,6-三取代嘧啶衍生物的合成及体外抗肿瘤活性研究[J]. 有机化学, 2017 , 37(10) : 2725 -2735 . DOI: 10.6023/cjoc201705013
With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. 40 2,4,6-trisubstituted pyrimidine derivatives bearing chalcone moiety were synthesized via cyclization, chlorination, substitution with benzoylacetate and ethylacetoacetate as the starting materials. The structures of target products were confirmed by 1H NMR, I3C NMR and HRMS. 2,4,6-Trisubstituted pyrimidine derivatives bearing chalcone moiety were evaluated for anticancer activity on four human cancer cell lines including EC-109, MGC-803, HepG-2 and MDA-MB-231 by CCK-8 (cell counting Kit-8) assay. Among them, (E)-1-(4-((2-(((1H-benzo[d]imidazol-2-yl)methyl)thio)-6-methylpyrimidin-4-yl)amino)-phe-nyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (13u) were more cytotoxic against MGC-803 and MDA-MB-231 cell lines, with IC50 values of 0.99 and 1.77 μmol·L-1, respectively.
Key words： 2,4,6-trisubstituted pyrimidine; chalcone; antitumor
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