Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (1): 310-317.DOI: 10.6023/cjoc202007067 Previous Articles     Next Articles



张洋a,b, 张路野a,b, 王继宽a,b, 刘丽敏a,b, 王涛a,b, 栗娜a,b, 汪正捷a,b, 刘秀娟a,b, 陈雅欣a,b, 赵丹琳a,b, 郑甲信a,c, 单丽红a,b,c,*(), 刘宏民a,b,c,d,*(), 张秋荣a,b,c,*()   

  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协同创新中心 郑州 450001
    c 教育部药物关键制备技术重点实验室 郑州 450001
    d 食管癌防治国家重点实验室 郑州 450052
  • 收稿日期:2020-07-29 修回日期:2020-08-26 发布日期:2020-08-31
  • 通讯作者: 单丽红, 刘宏民, 张秋荣
  • 作者简介:
    * Corresponding authors. E-mail: ; ;
  • 基金资助:
    国家自然科学基金(81773562); 国家蛋白质研究项目(2018YFE0195100); 省部共建食管癌防治国家重点实验室资助的开放基金(K2020000X)

Design, Synthesis and Antitumor Activity Evaluation Research of Novel 2,4,6-Substituted Pyrimidine Derivatives

Yang Zhanga,b, Luye Zhanga,b, Jikuan Wanga,b, Limin Liua,b, Tao Wanga,b, Na Lia,b, Zhengjie Wanga,b, Xiujuan Liua,b, Yaxin Chena,b, Danlin Zhaoa,b, Jiaxin Zhenga,c, Lihong Shana,b,c,*(), Hongmin Liua,b,c,d,*(), Qiurong Zhanga,b,c,*()   

  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 Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001
    d State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou 450052
  • Received:2020-07-29 Revised:2020-08-26 Published:2020-08-31
  • Contact: Lihong Shan, Hongmin Liu, Qiurong Zhang
  • Supported by:
    the National Natural Science Foundation of China(81773562); the National Key Research Program of Proteins(2018YFE0195100); the Openning Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment(K2020000X)

With the expectation to find out novel and effective anti-tumor agents, a series of novel 2,4,6-substituted pyrimidine derivatives were synthesized and evaluated for their anti-tumor activity against four human cancer cells [SW-620 (human colon cancer cells), PC-3 (human prostate cancer cells), A549 (Human non-small cell lung cancer cells), MGC-803 (human gastric cancer cells)] using methyl thiazolyl tetrazolium (MTT) assay. Among tested compounds, N-((4-ethylphenyl)- carbamoyl)-2-((4-( p-tolylamino)-6-(trifluoromethyl)pyrimidin-2-yl)thio)acetamide (5i), 2-((4-((4-ethoxyphenyl)amino)-6-(tri- fluoromethyl)pyrimidin-2-yl)thio)- N-((4-ethylphenyl)carbamoyl)acetamide (5o) and N-((4-ethylphenyl)carbamoyl)-2-((4-((4- methoxyphenyl)amino)-6-(trifluoromethyl)pyrimidin-2-yl)thio)acetamide (5r) displayed strong antiproliferative activity on 4 tested cancer cell lines. In particular, compound5r has the highest inhibitive activity, and possessed the lowest IC50 value of 1.46 μmol/L towards SW-620 cells. Further mechanism research shows that compound5rinduces SW-620 apoptosis, arrests cell cycle at S phase. Molecular docking reveals that5r can bind well to the active site of epidermal growth factor receptor (EG-FR), and may be considered as a promising compound amenable for further investigation for the development of new anticancer agents.

Key words: pyrimidine derivative, synthesis, antitumor activity, cell cycle, apoptosis