Synthesis, Characterization and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives asEpidermal Growth Factor Receptor Inhibitors

doi:10.1007/s40242-015-5202-3

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (6): 936-941.doi: 10.1007/s40242-015-5202-3

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Synthesis, Characterization and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives asEpidermal Growth Factor Receptor Inhibitors

SUN Bing¹, YIN Xiu'e¹, ZHANG Jin², HUANG Jian^1,2, XU Yue¹, ZHANG Furong¹, WANG Jinhui^1,2, WANG Guoqing¹, HU Chun¹

1. Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2015-05-20 Revised:2015-08-27 Online:2015-11-01 Published:2015-09-14
Contact: HU Chun E-mail:chunhu@syphu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.21342006) and the Program for the Innovative Research Team of the Ministry of Education of China(No.IRT_14R36).

Abstract

Abstract:

Based on the molecular docking studies, which were performed to position Erlotinib and the target compounds into the active site of the epidermal growth factor receptor(EGFR) to determine the probable binding model, a novel series of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as the novel potential EGFR kinase inhibitors was designed and synthesized. The antitumor activity of all the target compounds against human pulmonary carcinoma cell line A549 has been screened. Of all the target compounds, 4-[2-(1-piperidyl)carbonylmethoxyl- phenthio]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine(7j) demonstrated the most potent antitumor activity. Several of the target compounds exhibited moderate antitumor activity. The preliminary structure-activity relationships of some target compounds were summarized.

Key words: Antitumor activity, Docking, Epidermal growth factor receptor(EGFR)

SUN Bing, YIN Xiu'e, ZHANG Jin, HUANG Jian, XU Yue, ZHANG Furong, WANG Jinhui, WANG Guoqing, HU Chun. Synthesis, Characterization and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives asEpidermal Growth Factor Receptor Inhibitors[J]. Chemical Research in Chinese Universities, 2015, 31(6): 936-941.

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Synthesis, Characterization and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives asEpidermal Growth Factor Receptor Inhibitors

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