Synthesis and Biological Evaluation of N-(5-(2,5-dimethyl-phenoxy)-2,2-dimethylpentyl)-benzamide Derivatives as Novel Farnesoid X Receptor (FXR) Antagonist

Author(s): Siyun Nian, Zhenpeng Yu, Xiangduan Tan, Xia Gan, Mohan Huang, Yihuan Zhou, Guoping Wang*.

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 9 , 2018

Submit Manuscript
Submit Proposal

Graphical Abstract:


Background: Dyslipidemia is a serious threat to human health. The objective of our research was to develop effective FXR antagonists against dyslipidemia.

Methods: Herein we describe the design, synthesis of 37 N-(5-(2,5-dimethylphenoxy)-2,2- dimethylpentyl)-benzamide derivatives and evaluated for their FXR inhibition ability compared to GS and SIPI-7623.

Results: Structure–activity relationship analyses indicated that compounds containing hydroxyl on the right side of the phenyl were more effective than those without hydroxyl. Compound BI-24 was identified to have the most potent antagonic activity with an IC50 value of 10.8 µM for FXR, exhibited no cytotoxicity on HepG2 cells and reduced levels of TC, TG, LDL-C for 36%, 69%, and 32% on serum, respectively.

Conclusion: Compound BI-24 may be developed to a potential agent for the treatment of dyslipidemia.

Keywords: Hypolipidemic activity, FXR antagonists, synthesis, structure activity relationship, gugglesterone, molecular docking.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2018
Page: [923 - 936]
Pages: 14
DOI: 10.2174/1570180815666171226150403
Price: $58

Article Metrics

PDF: 20
PRC: 1