Design, Synthesis and Biological Evaluation of Small-Molecule Inhibitors of Signal Transducer and Activator of Transcription#br#
3 (STAT3) Signaling Pathway

doi:10.6023/cjoc201602030

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (8): 1854-1862.DOI: 10.6023/cjoc201602030 Previous Articles Next Articles

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信号转导及转录激活因子3(STAT3)信号通路小分子抑制剂的设计、合成及其生物活性研究

高顶顶, 包可婷, 张鸣鸣, 李英霞

复旦大学药学院上海 201203

收稿日期:2016-02-27 修回日期:2016-03-27 发布日期:2016-04-26
通讯作者: 李英霞 E-mail:liyx417@fudan.edu.cn
基金资助:
国家自然科学基金（No. 81473075）资助项目.

Design, Synthesis and Biological Evaluation of Small-Molecule Inhibitors of Signal Transducer and Activator of Transcription#br# 3 (STAT3) Signaling Pathway

Gao Dingding, Bao Keting, Zhang Mingming, Li Yingxia

Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203

Received:2016-02-27 Revised:2016-03-27 Published:2016-04-26
Supported by:
Project supported by the National Natural Science Foundation of China (No. 81473075).

1. Design, Synthesis and Biological Evaluation of Small-Molecule Inhibitors of Signal Transducer and Activator of Transcription#br# 3 (STAT3) Signaling Pathway.PDF(2792KB)

Abstract

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) is involved in the occurrence and development of the tumors, and is regarded as an attractive therapeutic target for cancer therapy. Our laboratory discovered some STAT3 inhibitors containing benzothiazole scaffold through virtual screening before. In a continuing effort to develop more potential STAT3 inhibitors, twenty-one target compounds based on our identified hit compound (16v) were rational designed and synthesized. These structures were characterized by ¹H NMR, ¹³C NMR and HRMS. All the target compounds were tested for their inhibitory activity using a STAT3 luciferase reporter system. The results showed that many compounds displayed better activity than lead compound 16v in series I. However, compounds containing thiazolo[5,4-d]pyrimidine scaffold led to the loss of inhibitory activity. This may attributed to the losing of hydrogen bonding to Glu638.

Key words: benzothiazole, thiazolo[5,4-d]pyrimidine, STAT3 signaling pathway

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Gao Dingding, Bao Keting, Zhang Mingming, Li Yingxia. Design, Synthesis and Biological Evaluation of Small-Molecule Inhibitors of Signal Transducer and Activator of Transcription#br# 3 (STAT3) Signaling Pathway[J]. Chin. J. Org. Chem., 2016, 36(8): 1854-1862.

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信号转导及转录激活因子3(STAT3)信号通路小分子抑制剂的设计、合成及其生物活性研究

Design, Synthesis and Biological Evaluation of Small-Molecule Inhibitors of Signal Transducer and Activator of Transcription#br# 3 (STAT3) Signaling Pathway

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