含丙烯酰胺结构的喹唑啉衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of Novel Quinazoline Derivatives Containing Acrylamide

作　　者：张路野 张洋 汪正捷 王涛 李二冬 刘丽敏 刘秀娟 郑甲信[1,2] 可钰 单丽红[1,4] 刘宏民 张秋荣[1,2,4] Zhang Luye;Zhang Yang;Wang Zhengjie;Wang Tao;Li Erdong;Liu Limin;Liu Xiujuan;Zheng Jiaxin;Ke Yu;Shan Lihong;Liu Hongmin;Zhang Qiurong(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation of Henan Province,Zhengzhou 450001;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou 450052;Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education,Zhengzhou 450001)

机构地区：[1]郑州大学药学院,郑州45000 [2]新药创制与药物安全性评价河南省协同创新中心,郑州450001 [3]省部共建食管癌防治国家重点实验室,郑州450052 [4]教育部药物制备关键技术重点实验室,郑州450001

出　　处：《有机化学》2020年第9期2804-2810,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.U1904163);省部共建食管癌防治国家重点实验室开放基金(No.K2020000X)资助项目。

摘　　要：为了寻找高效低毒的抗肿瘤药物,设计并合成了一系列新型的含N-(3-丙烯酰胺苯基)乙酰胺结构的喹唑啉类衍生物,并采用噻唑蓝(MTT)法测定了目标化合物对H1975(人肺腺癌细胞系),PC-3(人前列腺癌细胞系),MGC-803(人胃癌细胞系)三种肿瘤细胞的抗增殖活性.结果显示大部分化合物具有较好的抗肿瘤活性,其中N-(3-(2-((4-((4-氯苯基)氨基)-7-甲氧基喹唑啉-6-基)氧基)乙酰氨基)苯基)丙烯酰胺(13j)对H1975,MGC-803两种细胞显示出最好的抗增殖活性,IC50值分别为(6.77±0.65)和(4.06±0.34)μmol/L,其活性均优于阳性对照品吉非替尼,为抗肿瘤药物的研究提供了线索.In order to find efficient and low toxicity anti-tumor drugs,a series of novel quinazoline derivatives containing N-(3-aminophenyl)acrylamide were synthesized and their antiproliferative activities were evaluated against three human cancer cell lines(H1975,PC-3,MGC-803)by using methyl thiazolyl tetrazolium(MTT)assay.The results showed that most compounds exhibited better antiproliferative activities against the four human tumor cell lines.Among them,N-(3-(2-((4-((4-chlorophenyl)amino)-7-methoxy-quinazolin-6-yl)oxy)acetamido)phenyl)acrylamide(13 j)showed the best antiproliferative activity against H1975 and MGC-803 cancer cell lines with IC50 values of(6.77±0.65)and(4.06±0.34)μmol/L,respectively.Its activity was better than the positive control gefitinib.In a nutshell,this work provides clues to discover antitumor agent based on the quinazoline scaffold.

关 键 词：丙烯酰胺 喹唑啉 合成 抗肿瘤活性 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]