基于HER_2受体的新型喹唑啉衍生物的合成及其抗肿瘤活性

Synthesis and Antitumor Activities of Novel Quninazoline Derivatives Based on HER_2 Receptor

以取代4-[(4-硝基苯氧基)亚甲基]哌啶为原料,经还原、取代、suzuki和加成4步反应合成了6个新型的喹唑啉衍生物(5a^5f),其结构经1H NMR和ESI-MS表征。用MTT法考察了5a^5f对人脐静脉内皮细胞(HUVEC),人肺癌细胞(A-549),乳腺癌细胞(MCF-7)和人早幼粒白血病细胞(HL-60)的体外活性抑制活性。结果表明:环丙基【4-【【4-【【6-【5-{[(2-甲磺酰基乙基)氨基]甲基}呋喃-2-基】喹唑啉-4-基】氨基】苯氧基】甲基】哌啶-1-基】甲基酮(5b)抑制活性最好,其IC50分别为0.55μg·m L-1,0.18μg·m L-1,0.27μg·m L-1和5.24μg·m L-1,优于阳性对照药拉帕替尼。

Six novel quinazoline derivatives（5a - 5f） were synthesized by a four-step reaction of re- duction, substitution, Suzuki and addition from substituted 4-[ （4-nitro phenoxy） methyl] piperidine. The structures were characterized by 1H NMR and ESI-MS. The in vitro antitumor activities of 5a - 5f against HUVEC, A-549, MCF-7 and HL-50 were investgated by MTr method. The results showed that cyclopropy[ 4-[ [4-[ [ 6-[ 5-I [ （2-methylsulfonylethyl） amino ] methyl} furan-2-yl ] quinazolin-4- yl ] amino ] phenoxy ] methyl] piperidin-1 -yl ] methanone （Sb） exhibited better antitumor activities than Lapatinib. The ICs0 of 5b was 0.55 μg·mL^-1 , 0.18μg·mL^-1 , 0.27μg·mL^-1 and 5.24 μg·mL^-1, respectively.