Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists

doi:10.6023/cjoc201701049

Chin. J. Org. Chem. ›› 2017, Vol. 37 ›› Issue (9): 2385-2391.DOI: 10.6023/cjoc201701049 Previous Articles Next Articles

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新型八氢吡咯[3,2-c]吡啶衍生物作为趋化因子受体(CCR5)抑制剂的设计、合成及生物活性研究

王雨捷^a, Upul Halambage^c, 曾程初^a, 胡利明^a,b

a 北京工业大学生命科学与生物工程学院北京 100124;
b 北京工业大学环境与病毒肿瘤学北京重点实验室北京 100124;
c Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center Nashville 37232

收稿日期:2017-02-13 修回日期:2017-04-03 发布日期:2017-05-02
通讯作者: 胡利明 E-mail:huliming@bjut.edu.cn
基金资助:
国家自然科学基金（No.21272020）、环境与病毒肿瘤学北京市重点实验室资助项目.

Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists

Wang Yujie^a, Halambage Upul^c, Zeng Chengchu^a, Hu Liming^a,b

a College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124;
b Beijing Key Laboratory of Environmental and Viral Oncology, Beijing University of Technology, Beijing 100124;
c Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville 27232

Received:2017-02-13 Revised:2017-04-03 Published:2017-05-02
Contact: 10.6023/cjoc201701049 E-mail:huliming@bjut.edu.cn

1. Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists.PDF(1274KB)

Abstract

A series of novel octahydro-1H-pyrrolo[3,2-c]pyridine derivatives were designed and synthesized as C-C chemokine receptor type 5 (CCR5) antagonists, and their biological activity of anti-human immunodeficiency virus type 1 (HIV-1) is evaluated. A majority of these compounds showed anti-HIV-1 activities. Octahydro-1H-pyrrolo[3,2-c]pyridine derivative 19c exhibited potency against HIV-1 replication less than 1 μmol·L^-1. Function assay was employed and the result showed that there were other drug targets for HIV-1 inhibition besides CCR5. In addition, the preliminary structure-activity relationship (SAR) of these compounds was rationalized by docking studies.

Key words: HIV-1, CCR5 antagonists, piperidine derivatives, structure-activity relationships

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Wang Yujie, Halambage Upul, Zeng Chengchu, Hu Liming. Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists[J]. Chin. J. Org. Chem., 2017, 37(9): 2385-2391.

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新型八氢吡咯[3,2-c]吡啶衍生物作为趋化因子受体(CCR5)抑制剂的设计、合成及生物活性研究

Design, Synthesis, and Biological Activity of Novel Octahydro-1Hpyrrolo[3,2-c]pyridine Derivatives as C-C Chemokine Receptor Type 5 (CCR5) Antagonists

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