含亚胺结构片段的喹唑啉酮衍生物的合成与抗肿瘤活性研究  

Synthesis and Studies of Anti-tumor Activities of Quinazolone Derivatives Containing Enamine Moiety

作　　者：鄢龙家 王琴 刘力[1] 乐意[1] YAN Long-jia;WANG Qin;LIU Li;LE Yi(School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China)

机构地区：[1]贵州大学药学院,贵州贵阳550025

出　　处：《化学试剂》2022年第1期52-58,共7页Chemical Reagents

基　　金：贵州大学科研项目(贵大人基合字[2019]15)。

摘　　要：设计并合成了一系列含亚胺结构片段的新型喹唑啉酮衍生物,最终的15个化合物结构经^(1)HNMR、^(13)CNMR和HR-MS确证,并评价了它们对野生型表皮生长因子受体酪氨酸激酶(EGFR^(wt))和两种人癌细胞株(A549、HepG2)的体外抗肿瘤活性。结果表明,部分化合物具有良好的活性,特别是化合物(E)-2-((4-((3,4-二氟亚苄基)氨基)苯氧基)甲基)-3-甲基喹唑啉-4(3 H)-酮对EGFR^(wt)激酶的IC_(50)达到0.037μmol/L,对A549和HepG2两种肿瘤细胞的IC_(50)值优于吉非替尼。A series of novel quinazoline derivatives containing enamine moiety were designed and synthesized.The structures of the final 15 compounds were confirmed by ^(1)HNMR,^(13)CNMR and HR-MS,and their antitumor activities against wild-type epidermal growth factor receptor tyrosine kinase(EGFR^(wt))and two human cancer cell lines(A549 and HepG2)in vitro were evaluated.The results showed that some compounds have good activity,especially the IC_(50) value of(E)-2-((4-((3,4-difluorobenzylidene)amino)phenoxy)methyl)-3-methylquinazolin-4(3 H)-one against EGFR^(wt) reached 0.037μmol/L,and its IC_(50) values against A549 and HepG2 tumor cells were better than Gefitinib.

关 键 词：喹唑啉酮 亚胺 合成 抗肿瘤 活性 

分 类 号：O622.31[理学—有机化学]