含三氟甲基的2,4-取代嘧啶衍生物的合成及抗肿瘤活性评价
收稿日期: 2019-03-13
修回日期: 2019-04-16
网络出版日期: 2019-04-26
基金资助
国家自然科学基金（No.81430085）、河南省自然科学基金（No.182300410321）资助项目.
Synthesis and Antitumor Activity Evaluation of 2,4-Substituted Py-rimidine Derivatives Containing Trifluoromethyl
Received date: 2019-03-13
Revised date: 2019-04-16
Online published: 2019-04-26
Supported by
Project supported by the National Natural Science Foundation of China (No. 81430085) and the Natural Science Foundation of Henan Province (No. 182300410321).
为了寻找高效的新型抗肿瘤药物，设计并合成了一系列新型含三氟甲基的2，4-取代嘧啶衍生物，并对目标化合物在EC-109（人食管癌细胞），MGC-803（人胃癌细胞），PC-3（人前列腺癌细胞）和HepG-2（人肝癌细胞）进行抗肿瘤活性评价，结果显示部分化合物对PC-3表现出中度至强效的抗肿瘤活性.其中，2-（（（4-（（1-甲基-1H-四唑-5-基）硫基）-6-（三氟甲基）嘧啶-2-基）硫基）甲基）苯并[d]噻唑（13w）对PC-3具有较强的抗肿瘤活性，IC50为1.76 μmol·L-1，抗肿瘤活性明显优于阳性对照药5-氟尿嘧啶.
关键词： 三氟甲基; 2,4-取代嘧啶衍生物; 抗肿瘤活性
孟娅琪 , 李二冬 , 张洋 , 刘栓 , 包崇男 , 杨鹏 , 张路野 , 张丹青 , 王继宽 , 陈雅欣 , 栗娜 , 辛景超 , 赵培荣 , 可钰 , 张秋荣 , 刘宏民 . 含三氟甲基的2,4-取代嘧啶衍生物的合成及抗肿瘤活性评价[J]. 有机化学, 2019 , 39(9) : 2541 -2548 . DOI: 10.6023/cjoc201903022
In order to find more effective antitumor drugs, a series of novel 2,4-substituted pyrimidine derivatives containing trifluoromethyl were designed, synthesized, and evaluated for antitumor activity aganist EC-109 (human esophageal cancer cell), MGC-803 (human gastric cancer cell), PC-3 (human prostate cancer cell) and HepG-2 (human liver cancer cell). The results showed that some compounds displayed moderate to potent antitumor activity against PC-3. Among them, 2-(((4-((1-methyl-1H-tetrazol-5-yl)thio)-6-(trifluoromethyl)pyrimidin-2-yl)thio)methyl)benzo[d]thiazole (13w) possesses strong antitu-mor activity against PC-3 with IC50 value of 1.76 μmol·L-1, and the antitumor activity is significantly better than the positive control drug of 5-fluorouracil.
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