Citation: Li Erdong, Meng Yaqi, Zhang Luye, Zhang Yang, Wang Jikuan, Zhang Danqing, Song Panpan, Xin Jingchao, Li Na, Zheng Jiaxin, Ke Yu, Liu Hongmin, Zhang Qiurong. Design, Synthesis and Antitumor Activity Evaluation of 4-Aminoquinazoline Derivatives Containing Urea Moiety[J]. Chinese Journal of Organic Chemistry, ;2019, 39(10): 2875-2881. doi: 10.6023/cjoc201903062 shu

Design, Synthesis and Antitumor Activity Evaluation of 4-Aminoquinazoline Derivatives Containing Urea Moiety

Li Erdong ^a,d ,
Meng Yaqi ^a,d ,
Zhang Luye ^a,b ,
Zhang Yang ^a,b ,
Wang Jikuan ^a,b ,
Zhang Danqing ^a,b ,
Song Panpan ^b,c ,
Xin Jingchao ^b,c ,
Li Na ^b,c ,
Zheng Jiaxin ^a,d ,
Ke Yu ^a,b,c,d,, ,
Liu Hongmin ^a,b,c,d,, ,
Zhang Qiurong ^a,b,c,d,,

a.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
b.
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450001
c.
Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou 450001
d.
Key Laboratory of Technology of Drug Preparation(Zhengzhou University), Ministry of Education, Zhengzhou 450001

Corresponding author: Ke Yu, ky@zzu.edu.cn Liu Hongmin, liuhm@zzu.edu.cn Zhang Qiurong, zqr409@yeah.net
Received Date: 27 March 2019
Revised Date: 20 May 2019
Available Online: 3 October 2019
Fund Project: Project supported by the National Natural Science Foundation of China (No. 81430085), the Natural Science Foundation of Henan Province (No. 182300410321) and the Technology Department Project of Henan Province (No. 182102310249)the National Natural Science Foundation of China 81430085the Technology Department Project of Henan Province 182102310249the Natural Science Foundation of Henan Province 182300410321

Figures(3)

In order to find new anti-tumor drugs with targeted therapeutic effect, a series of novel 4-aminoquinazoline derivatives bearing urea moiety were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines of MCF-7, MGC-803, SW620 and A549 using methyl thiazolyl tetrazolium (MTT) assay. Most of the target compounds exhibited excellent anti-tumor activity against the four human tumor cell lines. Among them, 2-((4-((3, 4, 5-trimethoxyphenyl)-amino)quinazolin-2-yl)-thio)-N-((3, 4, 5-trimethoxyphenyl)carbamoyl)acetamide (10p) showed the best antitumor activity against MGC-803, SW620 and A549 cancer cell lines with IC₅₀ values of (7.02±0.46), (6.00±0.78) and (7.04±1.11) μmol· L^-1, respectively. Its activity was comparable to the positive control of gefitinib. Molecular docking showed that compound 10p could bind well with EGFR, suggesting that it could be a potential antitumor agent.
- urea moiety,
- 4-aminoquinazoline,
- synthesis,
- antitumor activity
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