| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370849 | Bioorganic & Medicinal Chemistry Letters | 2011 | 4 Pages |
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.
Graphical abstractImproved stability in rat and human liver microsomes. Improved rat PK profile. Efficacy in rat model of anti-depressant activity.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Thorsten Oost, Gisela Backfisch, Swati Bhowmik, Marcel M. van Gaalen, Hervé Geneste, Wilfried Hornberger, Wilfried Lubisch, Astrid Netz, Liliane Unger, Wolfgang Wernet,