Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties
| Autor: | W. Lubisch, Astrid Netz, Wilfried Hornberger, Swati Bhowmik, Liliane Unger, Hervé Geneste, Wolfgang Wernet, Marcel M. van Gaalen, Thorsten Oost, Gisela Backfisch |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Vasopressin
Indoles Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry chemistry.chemical_compound Drug Discovery Animals Moiety Oxindole Receptor Molecular Biology Oxazole Arginine vasopressin receptor 1B Molecular Structure Organic Chemistry Biological activity Antidepressive Agents Oxindoles Rats Disease Models Animal chemistry Lactam Molecular Medicine Antidiuretic Hormone Receptor Antagonists Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:3828-3831 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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