Novel,potent, selective and brain penetrant vasopressin 1b receptor antagonists |
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Authors: | Hervé Geneste Swati Bhowmik Marcel M van Gaalen Wilfried Hornberger Charles W Hutchins Astrid Netz Thorsten Oost Liliane Unger |
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Institution: | 1. AbbVie Deutschland GmbH & Co. KG, Neuroscience Research, D-67008 Ludwigshafen, Germany;2. AbbVie, Structural Biologie, IL 60064-6101, USA |
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Abstract: | Herein we report the discovery of a novel oxindole-based series of vasopressin 1b (V1b) receptor antagonists. Introducing a substituted piperazine moiety and optimizing the southern and the northern aromatic rings resulted in potent, selective and brain penetrant V1b receptor antagonists. Compound 9c was found to be efficacious in a rat model of anti-depressant activity (3?mg/kg, ip). Interestingly, both moderate terminal half-life and moderate bioavailability could be achieved despite sub-optimal microsomal stability. |
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Keywords: | Vasopressin 1b V1b SSR149415 Oxindole |
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