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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 2: 417 - 422

DOI: https://doi.org/10.6023/cjoc201907016

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

  • Li Erdong ,
  • Meng Yaqi ,
  • Zhang Luye ,
  • Zhang Yang ,
  • Zhou Rui ,
  • Liu Limin ,
  • Li Nab ,
  • Xin Jingchao ,
  • Zheng Jiaxin ,
  • Shan Lihong ,
  • Liu Hongmin ,
  • Zhang Qiurong
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  • 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 date: 2019-07-08

  Revised date: 2019-10-14

  Online 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).

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Abstract

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

Cite this article

Li Erdong , Meng Yaqi , Zhang Luye , Zhang Yang , Zhou Rui , Liu Limin , Li Nab , Xin Jingchao , Zheng Jiaxin , Shan Lihong , Liu Hongmin , Zhang Qiurong . Synthesis and Antitumor Evaluation of 2,4,6-Trisubstituted Pyrimidine Derivatives Containing Benzothiazole Moiety[J]. Chinese Journal of Organic Chemistry, 2020 , 40(2) : 417 -422 . DOI: 10.6023/cjoc201907016

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