Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

doi:10.1007/s40242-015-5036-z

高等学校化学研究 ›› 2015, Vol. 31 ›› Issue (5): 766-773.doi: 10.1007/s40242-015-5036-z

Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

收稿日期:2015-01-27 修回日期:2015-03-16 出版日期:2015-10-01 发布日期:2015-04-13
通讯作者: ZHAO Yanfang, E-mail: yanfangzhao@126.com E-mail:yanfangzhao@126.com
基金资助:
Supported by the Program for Innovative Research Team of the Ministry of Education of the People's Republic of China and Program for Liaoning Innovative Research Team in University, China(No.IRT1073) and the Liaoning Excellent Talents in University of China(No.LJQ2013106).

Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2015-01-27 Revised:2015-03-16 Online:2015-10-01 Published:2015-04-13
Contact: ZHAO Yanfang, E-mail: yanfangzhao@126.com E-mail:yanfangzhao@126.com
Supported by:
Supported by the Program for Innovative Research Team of the Ministry of Education of the People's Republic of China and Program for Liaoning Innovative Research Team in University, China(No.IRT1073) and the Liaoning Excellent Talents in University of China(No.LJQ2013106).

摘要/Abstract

摘要：

A series of 6,7-dimethoxyquinazoline derivatives connected by diaryl urea scaffolds was designed, synthesized and their in vitro antitumor activities were evaluated. Most of them showed an excellent potency against the four tested cancer cell lines as compared with sorafenib. Particularly, a promising compound 20 was identified, which showed the most potent antitumor activities with IC₅₀ values of 0.08, 0.09, 0.16 and 0.19 μmol/L against H460, HT-29, MKN-45 and MDA-MB-231 cell lines, respectively. The structure-activity relationship(SAR) analysis indicated that compounds with dimethylamino or diethylamino group at the C4 position of 6,7-dimethoxyquinazoline moiety exhibited superior activities than compounds bearing morpholino groups.

关键词: 6,7-Dimethoxyquinazoline derivative, Diaryl urea scaffold, Cytotoxic activity

Abstract:

Key words: 6,7-Dimethoxyquinazoline derivative, Diaryl urea scaffold, Cytotoxic activity

HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang. Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety[J]. 高等学校化学研究, 2015, 31(5): 766-773.

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Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

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