Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors

Tang, Jun; Jones, Stacey A.; Jeffery, Jerry L.; Miranda, Sonia R.; Galardi, Cristin M.; Irlbeck, David M.; Brown, Kevin W.; McDanal, Charlene B.; Han, Nianhe; Gao, Daxin; Wu, Yongyong; Shen, Bin; Liu, Chunyu; Xi, Caiming; Yang, Heping; Li, Rui; Yu, Yajun; Sun, Yufei; Jin, Zhimin; Wang, Erjuan; Johns, Brian A.

Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors

Jun Tang^{1, *}, Stacey A. Jones¹, Jerry L. Jeffery¹, Sonia R. Miranda¹, Cristin M. Galardi¹, David M. Irlbeck¹, Kevin W. Brown¹, Charlene B. McDanal¹, Nianhe Han², Daxin Gao², Yongyong Wu², Bin Shen², Chunyu Liu², Caiming Xi², Heping Yang², Rui Li², Yajun Yu², Yufei Sun², Zhimin Jin², Erjuan Wang², Brian A. Johns¹

¹ GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA

² ShangPharma Discovery Chemistry Services, Zhangjiang High-tech Park, Pudong, Shanghai 201203, China

Article Information

Identifiers and Pagination:

Year: 2014
Volume: 8
First Page: 23
Last Page: 27
Publisher ID: TOMCJ-8-23
DOI: 10.2174/1874104501408010023

Article History:

Received Date: 23/5/2014
Revision Received Date: 14/7/2014
Acceptance Date: 17/7/2014
Electronic publication date: 3/9/2014
Collection year: 2014

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© Tang et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

^* Address correspondence to this author at the GlaxoSmithKline Research & Development, Research Triangle Park, NC 27709, USA; Tel: +1-919-483-4173; Fax: +1-919-315-6923; E-mail: jun.x.tang@gsk.com

A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganized ring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge to access this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes to macrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potency compared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series of HIV-1 maturation inhibitors will be discussed.

Keywords: Betulin derivative, HIV, macrocyclization, maturation inhibitor.

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RESEARCH ARTICLE

Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors

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