Bridged bicyclic vasopressin receptor antagonists with V 2-Selective or dual V 1a/V 2 activity

Abstract

The synthesis and biological testing of a novel series of nonpeptide vasopressin receptor antagonists, containing a bridged bicyclic nucleus, are reported. Variation of substituents (R 1–R 3) in general formula 3, and the configuration of the stereocenter, resulted in potent V 2-selective (e.g., 4) and balanced dual V 1a/V 2 (e.g., 10) compounds. Data from receptor binding, cell-based functional, and in vivo assays are presented.