Design and Synthesis of Novel Gefitinib Analogues with Improved Anti-tumor Activity

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2010 May 15

PMID 20466555

Citations 18

Authors

Xiaoqing Wu

Mingdong Li

Yang Qu

Wenhua Tang

Youguang Zheng

Jiqin Lian

Min Ji

Liang Xu

Affiliations

Soon will be listed here.

Abstract

There is an urgent need to design and develop new and more potent EGFR inhibitors with improved anti-tumor activity. Here we describe the design and synthesis of two series of 4-benzothienyl amino quinazolines as new analogues of the EGFR inhibitor Gefitinib. The anti-tumor activity of these novel Gefitinib analogues in 6 human cancer cell lines was examined. Compared with the parental Gefitinib, most of the new compounds show a markedly increased cytotoxicity to cancer cells. Furthermore, several of the series B compounds that side chains at position 7 contain either a methyl or ethyl group are potent pan-RTK inhibitors. Two representative compounds in this class, 15 and 17, have an enhanced capability to inhibit cancer cell growth and induce apoptosis in vitro and inhibit tumor formation in vivo in human cancer cells with high HER-2, as compared with the parental Gefitinib. Thus they may be promising lead compounds to be developed as an alternative for current Gefitinib therapy or for Gefitinb-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways.

Citing Articles

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