Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR)

Pyrrole[2,3-d]azepines have been identified as potent agonists of the farnesoid X receptor (FXR). Based on the planar X-ray crystal structure of WAY-362450 1 in the ligand binding domain and molecular modeling studies, non-planar reduced compounds were designed which led to agonists that exhibit high aqueous solubility and retain moderate in vitro potency.

Graphical abstractThe rational design and discovery of a new series of pyrrole[2,3-d]azepino FXR agonists with aqueous solubility and improved pharmaceutical properties is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide