title: Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties.
abstract: Herein we report the discovery of a novel series of vasopressin 1b (V1b) receptor antagonists, starting from potent but metabolically labile oxindole SSR149415. Masking the proline N,N-dimethyl amide moiety as an oxazole and attaching a benzylic amine moiety to the northern phenyl ring resulted in potent and selective V1b receptor antagonists with improved metabolic stability and improved pharmacokinetic properties in rat. Compound 18c was found to be efficacious in a rat model of anti-depressant activity.
authors: Abbott, Neuroscience Discovery, Ludwigshafen, Germany.
authors: Thorsten
authors: T
authors: Oost
authors: Gisela
authors: G
authors: Backfisch
authors: Swati
authors: S
authors: Bhowmik
authors: Marcel M
authors: MM
authors: van Gaalen
authors: Hervé
authors: H
authors: Geneste
authors: Wilfried
authors: W
authors: Hornberger
authors: Wilfried
authors: W
authors: Lubisch
authors: Astrid
authors: A
authors: Netz
authors: Liliane
authors: L
authors: Unger
authors: Wolfgang
authors: W
authors: Wernet