Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists
Date of Original Version
Farnesoid X receptor (FXR), a nuclear receptor mainly distributed in liver and intestine, has been regarded as a potential target for the treatment of various metabolic diseases, cancer and infectious diseases related to liver. Starting from two previously identified chalcone-based FXR antagonists, we tried to increase the activity through the design and synthesis of a library containing chalcones, flavones and chromenes, based on substitution manipulation and conformation (ring closure) restriction strategy. Many chalcones and four chromenes were identified as microM potent FXR antagonists, among which chromene 11c significantly decreased the plasma and hepatic triglyceride level in KKay mice.
Publication Title, e.g., Journal
European Journal of Medicinal Chemistry
Zhang, Guoning, Shuainan Liu, Wenjuan Tan, Ruchi Verma, Yuan Chen, Deyang Sun, Yi Huan, Qian Jiang, Xing Wang, Na Wang, Yang Xu, Chiwai Wong, Zhufang Shen, Ruitang Deng, Jinsong Liu, Yanqiao Zhang, and Weishuo Fang. "Synthesis and biological evaluations of chalcones, flavones and chromenes as farnesoid x receptor (FXR) antagonists." European Journal of Medicinal Chemistry 129, (2017): 303-309. doi: 10.1016/j.ejmech.2017.02.037.