有机化学 ›› 2019, Vol. 39 ›› Issue (9): 2541-2548.DOI: 10.6023/cjoc201903022 上一篇    下一篇

研究论文

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

孟娅琪a,b, 李二冬a,b, 张洋a,b, 刘栓a,b, 包崇男a,b, 杨鹏a,b, 张路野a,b, 张丹青a,b, 王继宽a,b, 陈雅欣a,b, 栗娜a,b, 辛景超a,b, 赵培荣a,b, 可钰a,b, 张秋荣a,b, 刘宏民a,b   

  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
  • 收稿日期:2019-03-13 修回日期:2019-04-16 出版日期:2019-09-25 发布日期:2019-04-26
  • 通讯作者: 可钰, 张秋荣, 刘宏民 E-mail:ky@zzu.edu.cn;zqr406@sina.com;liuhm@zzu.edu.cn
  • 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

Meng Yaqia,b, Li Erdonga,b, Zhang Yanga,b, Liu Shuana,b, Bao Chongnana,b, Yang Penga,b, Zhang Luyea,b, Zhang Danqinga,b, Wang Jikuana,b, Chen Yaxina,b, Li Naa,b, Xin Jingchaoa,b, Zhao Peironga,b, Ke Yua,b, Zhang Qiuronga,b, Liu Hongmina,b   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
  • Received:2019-03-13 Revised:2019-04-16 Online:2019-09-25 Published:2019-04-26
  • Contact: 10.6023/cjoc201903022 E-mail:ky@zzu.edu.cn;zqr406@sina.com;liuhm@zzu.edu.cn
  • 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

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.

Key words: trifluoromethyl, 2,4-substituted pyrimidine derivatives, antitumor activity