Synthesis and in vitro biological evaluation of novel quinazoline derivatives

被引：38

作者：

Zhang, Yaling ^{[1
,2
]}

Zhang, Ying ^{[1
,2
]}

Liu, Juan ^{[1
,2
]}

Chen, Li ^{[1
,2
]}

Zhao, Lijun ^{[1
,2
]}

Li, Baolin ^{[1
,2
]}

Wang, Wei ^{[1
,2
]}

机构：

[1] Endangered Crude Drugs Northwest China, Natl Engn Lab Resource Dev, Key Lab Minist Educ Med Resources & Nat Pharmaceu, Xian 710062, Peoples R China

[2] Shaanxi Normal Univ, Sch Chem & Chem Engn, Xian 710062, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 07期

基金：

中国国家自然科学基金;

关键词：

4-Arylamino-6-(5-substituted furan-2-yl)quinazoline; EGFR; Tyrosine kinase inhibitors; Anti-proliferation; CELL LUNG-CANCER; DUAL INHIBITOR; EGFR; GROWTH; LAPATINIB; RESISTANCE; GEFITINIB; MUTATIONS; DOCKING;

D O I：

10.1016/j.bmcl.2017.02.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 4-arylamino-6-(5-substituted furan-2-yl)quinazoline derivatives were designed, synthesized and evaluated on biological activities in vitro. Compound 2a, 3a and 3c exhibited highly anti-proliferation activities on all tested tumor cell lines including SW480, A549, A431 and NCI-H1975 cells. Especially, compound 2a not only exhibited strong anti-proliferation activities against the tumor cell lines which expressed wild type or mutant EGFR(L858R/T790M), but also showed the most potent inhibitory activity toward wild type EGFR (IC50 = 5.06 nM). The result of docking with EGFR suggested the binding mode of 2a was similar to that of lapatinib. While Western-blot analyses showed 2a obviously inhibited the activation of EGFR, Akt and Erk1/2 in lung cancer cells at indicated concentration. It is believed that this work would be very useful for developing a new series of TKIs targeting EGFR. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：1584 / 1587

页数：4

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