title: 2-Phenoxy-nicotinamides are potent agonists at the bile acid receptor GPBAR1 (TGR5).
abstract: Potency with potential: 2-Phenoxy-nicotinamides were identified as potent agonists at the GPBAR1 receptor, a target in the treatment of obesity, type 2 diabetes and metabolic syndrome. Extensive structure-activity relationship studies supported by homology modeling and docking resulted in the identification of optimized GPBAR1 agonists, potent against both human and mouse receptors, endowed with favorable physicochemical properties and good metabolic stability.
authors.affiliation: Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland. rainer_e.martin@roche.com
authors.forename: Rainer E
authors.initials: RE
authors.lastname: Martin
authors.forename: Caterina
authors.initials: C
authors.lastname: Bissantz
authors.forename: Olivier
authors.initials: O
authors.lastname: Gavelle
authors.forename: Christoph
authors.initials: C
authors.lastname: Kuratli
authors.forename: Henrietta
authors.initials: H
authors.lastname: Dehmlow
authors.forename: Hans G F
authors.initials: HG
authors.lastname: Richter
authors.forename: Ulrike
authors.initials: U
authors.lastname: Obst Sander
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Erickson
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.forename: Sherrie Lynn
authors.initials: SL
authors.lastname: Pietranico-Cole
authors.forename: Rubén
authors.initials: R
authors.lastname: Alvarez-Sánchez
authors.forename: Christoph
authors.initials: C
authors.lastname: Ullmer
mesh_terms: D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D009536:Niacinamide / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C473772:GPBAR1 protein, human; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D009536:Niacinamide; C037219:quinoline