Potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties

T Oost, G Backfisch, S Bhowmik, MM van Gaalen…

Index: Oost, Thorsten; Backfisch, Gisela; Bhowmik, Swati; Van Gaalen, Marcel M.; Geneste, Herve; Hornberger, Wilfried; Lubisch, Wilfried; Netz, Astrid; Unger, Liliane; Wernet, Wolfgang Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 12 p. 3828 - 3831

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Citation Number: 12

Abstract

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 ...