Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (2): 417-422.DOI: 10.6023/cjoc201907016 Previous Articles     Next Articles


李二冬a,d, 孟娅琪a,d, 张路野a,b, 张洋a,b, 周蕊a, 刘丽敏a, 栗娜b,c, 辛景超b,c, 郑甲信a,d, 单丽红a,b,c,d, 刘宏民a,b,c,d, 张秋荣a,b,c,d   

  1. a 郑州大学药学院 郑州 450001;
    b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001;
    c 河南省药物质量评价重点实验室 郑州 450001;
    d 教育部药物制备关键技术重点实验室 郑州 450001
  • 收稿日期:2019-07-08 修回日期:2019-10-14 发布日期:2019-10-25
  • 通讯作者: 张秋荣, 刘宏民, 单丽红;;
  • 基金资助:

Synthesis and Antitumor Evaluation of 2,4,6-Trisubstituted Pyrimidine Derivatives Containing Benzothiazole Moiety

Li Erdonga,d, Meng Yaqia,d, Zhang Luyea,b, Zhang Yanga,b, Zhou Ruia, Liu Limina, Li Nabb,c, Xin Jingchaob,c, Zheng Jiaxina,d, Shan Lihonga,b,c,d, Liu Hongmina,b,c,d, Zhang Qiuronga,b,c,d   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001;
    c Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001;
    d Key Laboratory of Technology of Drug Preparation, Ministry of Education, Zhengzhou 450001
  • Received:2019-07-08 Revised:2019-10-14 Published:2019-10-25
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. U1904163) and the National Key Research Program of Proteins (No. 2018YFE0195100).

In order to find high-efficiency antitumor drugs, a series of 2,4,6-trisubstituted pyrimidine derivatives containing benzothiazole moiety were designed, synthesized and evaluated for antitumor activities against four cancer cells (EC-109, human esophageal cancer cells; MGC-803, human gastric cancer cells; PC-3, human prostate cancer cells; HepG-2, human liver cancer cells), GES-1 (human normal gastric mucosal epithelial cells), and HEEC (human normal esophagus) using thiazolyl blue (MTT) method. The results showed that some compounds exhibited moderate to strong antitumor activities against MGC-803 and PC-3 cells. Among them, 2-(((4-(4-(pyridin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)-thio)methyl)benzo[d]thiazole (13h) and 2-(((4-(4-(pyrimidin-2-yl)piperazin-1-yl)-6-(trifluoromethyl)pyrimidin-2-yl)thio)-methyl)benzo[d]thiazole (13i) showed the most potent antitumor activities against PC-3 cells with IC50 values of 3.82 and 2.29 μmol/L, respectively. The toxicities of compounds 13h and 13i to GES-1 cells were significantly lower than the positive control 5-fluorouracil.

Key words: pyrimidine, benzothiazole, synthesis, antitumor activity