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  

Splicing of 6-Amino-4-anilinoquinazoline with 5-Fluorouracil-1-acetic Acid and Its Antitumor Activity

作　　者：梁光平 田芷 梁光焰 王道平[2] 杨俊 李敏[1] LIANG Guang-ping;TIAN Zhi;LIANG Guang-yan;WANG Dao-ping;YANG Jun;LI Min(Department of Pharmacy,Zunyi Medical and Pharmaceutical College,Zunyi 563006,China;The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences,Guiyang 550014,China)

机构地区：[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

出　　处：《精细化工中间体》2022年第2期20-23,63,共5页Fine Chemical Intermediates

基　　金：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)。

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-8c)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IC_(50)分别为1.98、18.71μmol/L。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■ were obtained through amidation reactions between 5-fluorouracil-1-acetic acid and the 6-amino-4-phenylamine quinazoline derivatives.Their structures were confirmed by1H NMR and MS.The inhibitory activity of compound■on HepG2,A549,Hela,MCF-7 and A549/DDP cells was investigated by MTT Assay while the inhibitory effects of compounds■on EGFR enzyme were investigated by ELISA.The results showed that compound■had a certain inhibitory effect on five kinds of cells,and the inhibitory effects of compound■on HepG2,A549 and A549/DDP were 1.85,1.47 and 2.07 times that of Erlotinib,and the IC_(50) on MCF-7 and Hela were 1.98 and 18.71 μmol/L,respectively.

关 键 词：5-氟尿嘧啶 喹唑啉 合成 抗肿瘤 

分 类 号：R914.5[医药卫生—药物化学]