Chinese Journal of Organic Chemistry >
Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives
Received date: 2015-03-22
Revised date: 2015-04-20
Online published: 2015-04-30
Supported by
Project supported by the Foundation of Heilongjiang Educational Committee.
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
Shen Minghui , Chen Shijie , Wang Xuewei , Gong Xianfeng , Zhang Hua . Synthesis and Cytotoxic Activity of 6-Modified Gefitinib Derivatives[J]. Chinese Journal of Organic Chemistry, 2015 , 35(8) : 1765 -1772 . DOI: 10.6023/cjoc201503032
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