第 52 卷第 2 期Vol. 52 No. 2
2022 年 4 月Apr 2022
所属栏目：医药及中间体

6-氨基-4-苯胺喹唑啉骨架与5-氟尿嘧啶-1-乙酸拼接合成及抗肿瘤活性研究
梁光平1，田 芷1，梁光焰2，王道平2，杨 俊1*，李 敏1 （1.遵义医药高等专科学校 药学系，贵州 遵义 563006；2.贵州省中国科学院天然产物化学重点实验室，贵州 贵阳 550014）
摘　要：以2-氨基-5-硝基苯腈和三种卤代苯胺为原料，通过缩合、环化、还原3步反应制得三种6-氨基-4-苯胺喹唑啉衍生物，再与5-氟尿嘧啶-1-乙酸通过酰胺化反应得到三种未见文献报道的目标产物（8a~8c），其结构经1H NMR和MS确认。利用MTT法考察化合物8a~8c对HepG2、A549、Hela、MCF-7、A549/DDP细胞的抑制活性，利用ELISA法检测化合物8a~8c对A549细胞上清液中EGFR酶的抑制作用。结果表明，化合物8a~8c对五种细胞都具有一定的抑制作用，化合物8a对HepG2、A549、A549/DDP细胞的抑制作用分别是厄洛替尼的1.85、1.47、2.07倍，对MCF-7、Hela细胞的IC50分别为1.98、18.71 μmol/L。
关键词：5-氟尿嘧啶；喹唑啉；合成；抗肿瘤
中图分类号：R914.5　　文献标识码：A　　文章编号：1009-9212（2022）02-0020-04
Splicing of 6-Amino-4-anilinoquinazoline with 5-Fluorouracil-1-acetic Acid and Its Antitumor Activity
LIANG Guang-ping1, TIAN Zhi1, LIANG Guang-yan2, WANG Dao-ping2, YANG Jun1*, LI Min1 (1. Department of Pharmacy, Zunyi Medical and Pharmaceutical College, Zunyi 563006, China; 2.The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China)
Abstract：Three 6-amino-4-phenylamine quinazoline derivatives were synthesized from 2-amino-5-nitrobenzonitrile and three aniline derivatives through a series of reactions including condensation, cyclization and reduction. Subsequently, three target ligands (8a~8c) were obtained through amidation reactions between 5-fluorouracil-1-acetic acid and the 6-amino-4-phenylamine quinazoline derivatives. Their structures were confirmed by 1H NMR and MS. The inhibitory activity of compound 8a~8c on HepG2, A549, Hela, MCF-7 and A549/DDP cells was investigated by MTT Assay while the inhibitory effects of compounds 8a~8c on EGFR enzyme were investigated by ELISA. The results showed that compound 8a~8c had a certain inhibitory effect on five kinds of cells, and the inhibitory effects of compound 8a on HepG2, A549 and A549/DDP were 1.85, 1.47 and 2.07 times that of Erlotinib, and the IC50 on MCF-7 and Hela were 1.98 and 18.71 μmol/L, respectively.
Key words：5-fluorouracil; quinazoline; synthesis; anti-tumor
基金项目：贵州省科学技术基金资助项目（黔科合基础［2019］1356号），遵义医药高等专科学校博士科研启动项目（遵医专科合BS2018001号）。
作者简介：梁光平（1988—），男，贵州遵义人，副教授，博士，研究方向：化学成分的结构修饰及其活性研究（E-mail:guangping_liang@aliyun.com）。
联 系 人：杨 俊，讲师，研究方向：合成药物化学（E-mail:420625539@qq.com）。
收稿日期：2022-02-09