高等学校化学学报

高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (10): 2249.doi: 10.7503/cjcu20111217

• 有机化学 • 上一篇    下一篇

3-[(4'-吗啉基)-羰基或乙氧羰基]-4-苯氨基喹啉化合物的合成及抗肿瘤活性

刘丹1, 朱秀杰1, 姜梦1, 陈虹2, 兰帅鹏1   

  1. 1. 沈阳化工大学制药工程教研室, 沈阳 110142;
    2. 中国人民武装警察部队医学院生药教研室, 天津 300162
  • 收稿日期:2011-12-26 出版日期:2012-10-10 发布日期:2012-09-12
  • 通讯作者: 刘 丹, 女, 博士, 副教授, 主要从事药物化学研究. E-mail: liudan20040318@163.com E-mail:liudan20040318@163.com

Synthesis and Antitumor Activities of 3-[(4'-Morpholine)-carbonyl or ethoxycarbonyl]-4-anilinoqunolines

LIU Dan1, ZHU Xiu-Jie1, JIANG Meng1, CHEN Hong2, LAN Shuai-Peng1   

  1. 1. Department of Pharmaceutical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China;
    2. Department of Pharmacognosy, Medical College of Chinese People's Armed Police Forces, Tianjin 300162, China
  • Received:2011-12-26 Online:2012-10-10 Published:2012-09-12

PDF (PC)

被引次数

11

摘要：

以间氯苯胺与乙氧基亚甲基丙二酸二乙酯(EMME)为原料, 经缩合、 高温环合、 水解、 氯代和亲核取代等反应设计并合成了16个3位为(4'-吗啉)-羰基或乙氧羰基的4-苯氨基喹啉化合物(Ⅰ1~Ⅰ10, Ⅱ1~Ⅱ6). 目标化合物结构经MS及1H NMR确证. 以MTT法, 采用表皮生长因子受体(EGFRs)高表达的人癌细胞(HeLa, HepG2, BGC-823)对目标化合物进行活性测试, 结果表明, 该类化合物对HeLa, HepG2和BGC-823细胞增殖具有一定程度的抑制作用. 其中化合物Ⅱ4~Ⅱ6 对 HepG2 细胞抑制作用较强, 化合物Ⅱ1和Ⅱ5对BGC-823细胞抑制作用较强. 初步探讨了化合物结构与生物活性的关系.

关键词: 4-苯氨基喹啉, 肿瘤, 表皮生长因子受体, 酪氨酸激酶, 抑制剂

Abstract:

Sixteen new 4-anilinoqunolines with 4'-morpholine-carbonyl group or ethoxycarbonyl group at C3 position(Ⅰ1-Ⅰ10, Ⅱ1-Ⅱ6) were designed and synthesized from 3-chlorobenzenamine and ethoxymethylene malonic diethyl ester(EMME) by the condensation, high-temperature cyclization, hydrolysis and nucleophilic substitution reaction. Their structures were confirmed by MS and 1H NMR analysis. The antitumor activities of these compounds were evaluated by MTT assay in HeLa, HepG2 and BGC-823 cells expressing high levels of epidermal growth factor receptor(EGFR). These compounds exhibited somewhat inhibitory activities against the three cancer cells. Among them, compounds Ⅱ4-Ⅱ6 had stronger inhibition on HepG2 cell and Ⅱ1, Ⅱ5 had stronger activity on BGC-823 cell. Preliminary structure-activity relationship was also discussed.

Key words: 4-Anilinoquinoline, Tumor, Epidermal growth factor receptor(EGFR), Tyrosine kinase, Inhibitor

中图分类号: 

TrendMD: