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.
Mehlmann
John F
JF
Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Crawley
Matthew L
ML
Lundquist
Joseph T
JT
Unwalla
Ray J
RJ
Harnish
Douglas C
DC
Evans
Mark J
MJ
Kim
Callain Y
CY
Wrobel
Jay E
JE
Mahaney
Paige E
PE
D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000099150:Receptor, Farnesoid X-Activated
D001381:Azepines; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated