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  

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

作　　者：汪正捷 戴洪林 司晓杰 高潮 刘丽敏 张路野 张洋 宋亚丹[1,2] 赵培荣 郑甲信 可钰[1,2] 刘宏民[1,2,3,4] 张秋荣[1,2,4] Wang Zhengjie;Dai Honglin;Si Xiaojie;Gao Chao;Liu Limin;Zhang Luye;Zhang Yang;Song Yadan;Zhao Peirong;Zheng Jiaxin;Ke Yu;Liu Hongmin;Zhang Qiurong(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Collaborative Innovation Center of New Drug Research and Safety Evaluation,Zhengzhou University,Zhengzhou 450001;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou University,Zhengzhou,450052;Key Laboratory of Advanced Drug Preparation Technologies,Ministry of Education of China,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]郑州大学药学院,郑州450001 [2]郑州大学新药研究与安全评价协同创新中心,郑州450001 [3]郑州大学食管癌防治国家重点实验室,郑州450052 [4]郑州大学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》2022年第1期249-256,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.U1904163);国家蛋白质研究项目(No.2018YFE0195100);省部共建食管癌防治国家重点实验室资助的开放基金(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三氟甲基基团的2,4,6-三取代喹唑啉喹唑啉类衍生物,并采用噻唑蓝(MTT)比色法测定目标化合物对人前列腺癌细胞系(PC-3)、人乳腺癌细胞系(MCF-7)、人食管癌细胞系(Eca-109)、人胃癌细胞系(MGC-803)、人未分化胃癌细胞系(HGC-27)、人非小细胞肺癌细胞系(A549)和人非小细胞肺癌细胞系(H1975)的抗肿瘤活性.结果显示部分化合物表现出中度至强效的抗肿瘤活性,其中N-(3-溴苯基)-6-甲氧基-2-((4-(三氟甲基)苄基)硫代)喹唑啉-4-胺(16l)对PC-3细胞具有最好的抗肿瘤活性,IC_(50)值为(2.22±0.15)μmol/L,抗肿瘤活性明显优于阳性对照品吉非替尼.此外,化合物16l对PC-3细胞以浓度依赖与时间依赖的方式诱导其凋亡.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 IC_(50) 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.

关 键 词：三氟甲基 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]