PlumX Metrics
Embed PlumX Metrics

Design, synthesis, and biological studies of novel sulfonamide derivatives as farnesoid X receptor agonists

European Journal of Medicinal Chemistry, ISSN: 0223-5234, Vol: 258, Page: 115614
2023
  • 0
    Citations
  • 0
    Usage
  • 6
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Farnesoid X receptor (FXR) is considered as a promising target for the treatment of NASH. Although many non-steroidal FXR agonists have been reported, the structure types are quite scarce and mainly limited to the isoxazole scaffold derived from GW4064. Therefore, it is crucial to expand the structure types of FXR agonist to explore wider chemical space. In this study, the structure-based scaffold hopping strategy was performed by hybrid FXR agonist 1 and T0901317, which resulted in the discovery of sulfonamide FXR agonist 19. Molecular docking study reasonably explained the SAR in this series, and compound 19 fitted well with the binding pocket in a similar mode to the co-crystal ligand. In addition, compound 19 exhibited considerable selectivity against other nuclear receptors. In NASH model, compound 19 alleviated the typical histological features of fatty liver, including steatosis, lobular inflammation, ballooning, and fibrosis. Moreover, compound 19 exhibited acceptable safety profiles with no acute toxicity to major organ. These results suggested that the novel sulfonamide FXR agonist 19 might be a promising agent for the treatment of NASH.

Bibliographic Details

Wang, Wenxin; Cao, Zhijun; Yang, Zhongcheng; Chen, Ya; Yao, Huixin; Zhou, Danting; Ou, Peixin; Huang, Wanqiu; Jiao, Shixuan; Chen, Siliang; Chen, Lianru; Liu, Yuxia; Mao, Jianming; Xie, Jiayi; Xiang, Ruojing; Yang, Yuanqian; Chen, Yisi; Yang, Yonghong; Tan, Liyun; Tang, Haolong; Zhang, Luyong; Li, Zheng

Elsevier BV

Pharmacology, Toxicology and Pharmaceutics; Chemistry

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know