Next-generation spirobenzazepines : Identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies

Abstract We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 ( 2 ), which had advanced into preclinical development. Further structural modifications were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V 1a /V 2 receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation.