Conformationally constrained farnesoid X receptor (FXR) agonists: Alternative replacements of the stilbene

To further explore the optimum placement of the acid moiety in conformationally constrained analogs of GW 4064 1a, a series of stilbene replacements were prepared. The benzothiophene 1f and the indole 1g display the optimal orientation of the carboxylate for enhanced FXR agonist potency.

Graphical abstractTo further explore the optimum placement of the acid moiety in conformationally constrained analogs of GW 4064 1a, a series of stilbene replacements were prepared. The benzothiophene1f and the indole 1g display the optimal orientation of the carboxylate for enhanced FXR agonist potency.Figure optionsDownload full-size imageDownload as PowerPoint slide