Citation: He Haibing, Dai Hong, Gao Lixin, Zhang Haijun, Zou Zhenga, Yang Fan, Li Jia, Shi Yujun. Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B[J]. Chinese Journal of Organic Chemistry, ;2016, 36(11): 2670-2676. doi: 10.6023/cjoc201605018 shu

Design, Synthesis of Lithocholic Acid Mimics and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B

He Haibing ^a ,
Dai Hong ^a ,
Gao Lixin ^b ,
Zhang Haijun ^a ,
Zou Zhenga ^a ,
Yang Fan ^c,*,, ,
Li Jia ^b ,
Shi Yujun ^a,*,,

a.
College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019
b.
National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
c.
Shanghai Engineering Institute of Molecular Therapy and Medicinal Development (MTDD), School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062

Corresponding author: Yang Fan, fyang@chem.ecnu.edu.cn Shi Yujun, shyj123123@163.com
Received Date: 12 May 2016
Revised Date: 27 May 2016

Fund Project: the Initiating Fund for Introduced Talents of Nantong University 03080694the Science Fund for Young Scholar of Jiangsu Province BK20140425

Figures(4)

Protein tyrosine phosphatase-1B (PTP1B), a negative regulatory factor of insulin signaling, is recognized as a potent target for the therapy of diabetes. Aimed to provide new scaffold to the development of PTP1B inhibitors and disclose the relationship between configurations of certain positions (3, 4, 5, 6 and 23-position) on the steroidal skeleton and inhibitory activities against PTP1B, a class of lithocholic acid (LCA) mimics were designed and synthesized. In vitro bioassay against PTP1B showed that 3β-hydroxy-4-ene-cholanic acid (17) and 4, 4-dimethyl-3β-hydroxy-5-ene-cholanic acid (19) had activities higher than LCA, reaching (8.50±1.21) and (6.27±1.03) μmol·L^-1, respectively. Docking analysis of compounds 17 and 19 illuminated the binding modes to PTP1B. This study provided compounds with new scaffold and valuable structure-activity-relationship (SAR) information for the further study of PTP1B inhibitors.
- PTP1B inhibitor,
- steroid,
- lithocholic acid mimics,
- synthesis
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