Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (1): 249-256.DOI: 10.6023/cjoc202107026 Previous Articles     Next Articles

ARTICLES

含三氟甲基的2,4,6-三取代喹唑啉衍生物的合成及抗肿瘤活性研究

汪正捷a,b, 戴洪林a,b, 司晓杰a,b, 高潮a,b, 刘丽敏a,b, 张路野a,b, 张洋a,b, 宋亚丹a,b, 赵培荣a,b,c, 郑甲信a,b, 可钰a,b,*(), 刘宏民a,b,c,d,*(), 张秋荣a,b,d,*()   

  1. a 郑州大学药学院 郑州 450001
    b 郑州大学 新药研究与安全评价协同创新中心 郑州 450001
    c 郑州大学 食管癌防治国家重点实验室 郑州 450052
    d 郑州大学 教育部药物制备关键技术重点实验室 郑州 450001
  • 收稿日期:2021-07-12 修回日期:2021-08-13 发布日期:2021-08-28
  • 通讯作者: 可钰, 刘宏民, 张秋荣
  • 基金资助:
    国家自然科学基金(U1904163); 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)

Synthesis and Antitumor Activity of 2,4,6-Trisubstituted Novel Quinazoline Derivatives Containing Trifluoromethyl

Zhengjie Wanga,b, Honglin Daia,b, Xiaojie Sia,b, Chao Gaoa,b, Limin Liua,b, Luye Zhanga,b, Yang Zhanga,b, Yadan Songa,b, Peirong Zhaoa,b,c, Jiaxin Zhenga,b, Yu Kea,b(), Hongmin Liua,b,c,d(), Qiurong Zhanga,b,d()   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
    b Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450001
    c State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052
    d Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001
  • Received:2021-07-12 Revised:2021-08-13 Published:2021-08-28
  • Contact: Yu Ke, Hongmin Liu, Qiurong Zhang
  • Supported by:
    National Natural Science Foundation of China(U1904163); National Key Research Program of Proteins(2018YFE0195100); Opening Fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment(K2020000X)

In order to find efficient and low toxicity antitumor drugs, a series of novel 2,4,6-trisubstituted quinazoline derivatives containing trifluoromethyl were synthesized and evaluated for their antitumor activities against human cancer cell lines (PC-3, MCF-7, Eca-109, MGC-803, HGC-27, A549, H1975) by using methyl thiazolyl tetrazolium (MTT) assay. Most of compounds exerted moderate to excellent antitumor activity against seven human cancer cells. Among them, N-(3-bromophenyl)-6-methoxy-2-((4-(trifluoromethyl)benzyl)thio)quinazolin-4-amine (16l) showed the best antitumor activity against PC-3 cancer cell line, with the IC50 values of (2.22±0.15) μmol/L, which was better than the positive control of gefitinib. At the same time, and compound 16l could dose-dependently and time-dependently induce PC-3 cells apoptosis.

Key words: trifluoromethyl, quinazoline, synthesis, antitumor activity