title: Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR).
abstract: 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.
authors.affiliation: Chemical Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Mehlmann
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Crawley
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Lundquist
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Unwalla
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Harnish
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Evans
authors.forename: Callain Y
authors.initials: CY
authors.lastname: Kim
authors.forename: Jay E
authors.initials: JE
authors.lastname: Wrobel
authors.forename: Paige E
authors.initials: PE
authors.lastname: Mahaney
mesh_terms: 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
chemical_list: D001381:Azepines; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated