Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives

doi:10.6023/cjoc201503032

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (8): 1765-1772.DOI: 10.6023/cjoc201503032 Previous Articles Next Articles

NOTE

6-位修饰的吉非替尼衍生物合成及细胞毒活性研究

沈明辉^a, 陈仕杰^a, 王雪微^a, 龚显峰^a,b, 张华^a,b

a 黑龙江大学功能有机重点实验室哈尔滨 150080;
b 国药一心制药有限公司长春 130012

收稿日期:2015-03-22 修回日期:2015-04-20 发布日期:2015-04-30
通讯作者: 张华 E-mail:zhanghua34@163.com
基金资助:
黑龙江省教育厅科学技术研究资助项目.

Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives

Shen Minghui^a, Chen Shijie^a, Wang Xuewei^a, Gong Xianfeng^a,b, Zhang Hua^a,b

a Key Laboratory of Applied Organic, Heilongjiang University, Harbin 150080;
b Sinopharm A-Think Pharmaceuticals Co., Ltd., Changchun 130012

Received:2015-03-22 Revised:2015-04-20 Published:2015-04-30
Supported by:
Project supported by the Foundation of Heilongjiang Educational Committee.

1. Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives.PDF(37023KB)

Abstract

Twenty-three derivatives of gefitinib have been synthesized by etherification and esterification of 4-(3-chloro-4-fluoroanilino)-6-hydroxy-7-methoxy quinazoline, which was prepared from 2-amino-4,5-dimethoxy-benzoic acid through the reactions of cyclization, selective demethylation, acetyl protection, chlorination, substitution with 3-chloro-4-fluoro-benzenamine and deprotection, respectively. The structures of the target compounds were characterized by IR,¹H NMR, ¹³C NMR and HRMS spectra. All the title compounds were evaluated for cytotoxic activity against human non-small-cell-lung cancer cells lines (A549) and human hepatoma cell lines (HepG2) by methyl thiazolyl tetrazolium (MTT) method. The results showed that the cytotoxic activities of compounds 7b, 7c, 7d, 8a, 8m against human non-small-cell-lung cancer cells lines and compounds 7c, 8m against human hepatoma cell lines were comparable to those of gifitinib.

Key words: gefitinib derivatives, synthesis, MTT assay

Cite this article

Shen Minghui, Chen Shijie, Wang Xuewei, Gong Xianfeng, Zhang Hua. Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives[J]. Chin. J. Org. Chem., 2015, 35(8): 1765-1772.

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6-位修饰的吉非替尼衍生物合成及细胞毒活性研究

Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives

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