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

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¹HNMR、¹³CNMR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IC₅₀达到0.037μmol/L,对A549和HepG2两种肿瘤细胞的IC₅₀值优于吉非替尼。

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

A series of novel quinazoline derivatives containing enamine moiety were designed and synthesized.The structures of the final 15 compounds were confirmed by ¹HNMR,¹³CNMR 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 IC₅₀ 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 IC₅₀ values against A549 and HepG2 tumor cells were better than Gefitinib.