Chinese Journal of Organic Chemistry ›› 2019, Vol. 39 ›› Issue (10): 2875-2881.DOI: 10.6023/cjoc201903062 Previous Articles     Next Articles



李二冬ad, 孟娅琪ad, 张路野ab, 张洋ab, 王继宽ab, 张丹青ab, 宋攀攀bc, 辛景超bc, 栗娜bc, 郑甲信ad, 可钰abcd*(), 刘宏民abcd*(), 张秋荣abcd*()   

  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:2019-03-27 修回日期:2019-05-20 发布日期:2019-06-03
  • 通讯作者: 可钰,刘宏民,张秋荣;;
  • 基金资助:
    国家自然科学基金(81430085);河南省自然科学基金(182300410321);河南省科技厅(No. 182102310249)

Design, Synthesis and Antitumor Activity Evaluation of 4-Aminoquinazoline Derivatives Containing Urea Moiety

Li, Erdongad, Meng, Yaqiad, Zhang, Luyeab, Zhang, Yangab, Wang, Jikuanab, Zhang, Danqingab, Song, Panpanbc, Xin, Jingchaobc, Li, Nabc, Zheng, Jiaxinad, Ke, Yuabcd*(), Liu, Hongminabcd*(), Zhang, Qiurongabcd*()   

  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 (Zhengzhou University), Ministry of Education, Zhengzhou 450001
  • Received:2019-03-27 Revised:2019-05-20 Published:2019-06-03
  • Contact: Ke, Yu,Liu, Hongmin,Zhang, Qiurong;;
  • Supported by:
    Project supported by the National Natural Science Foundation of China(81430085);the Natural Science Foundation of Henan Province(182300410321);the Technology Department Project of Henan Province(No. 182102310249)

In order to find new anti-tumor drugs with targeted therapeutic effect, a series of novel 4-aminoquinazoline derivatives bearing urea moiety were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines of MCF-7, MGC-803, SW620 and A549 using methyl thiazolyl tetrazolium (MTT) assay. Most of the target compounds exhibited excellent anti-tumor activity against the four human tumor cell lines. Among them, 2-((4-((3,4,5-trimethoxyphenyl)- amino)quinazolin-2-yl)-thio)-N-((3,4,5-trimethoxyphenyl)carbamoyl)acetamide (10p) showed the best antitumor activity against MGC-803, SW620 and A549 cancer cell lines with IC50 values of (7.02±0.46), (6.00±0.78) and (7.04±1.11) μmol? L –1, respectively. Its activity was comparable to the positive control of gefitinib. Molecular docking showed that compound 10p could bind well with EGFR, suggesting that it could be a potential antitumor agent.

Key words: urea moiety, 4-aminoquinazoline, synthesis, antitumor activity