Next-generation spirobenzazepines: Identification of RWJ-676070 as a balanced vasopressin V 1a/V 2 receptor antagonist for human clinical studies

…, DF McComsey, HC Zhang, JW Gunnet, R Look…

Index: Xiang, Min Amy; Rybczynski, Philip J.; Patel, Mona; Chen, Robert H.; McComsey, David F.; Zhang, Han-Cheng; Gunnet, Joseph W.; Look, Richard; Wang, Yuanping; Minor, Lisa K.; Zhong, H. Marlon; Villani, Frank J.; Demarest, Keith T.; Damiano, Bruce P.; Maryanoff, Bruce E. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 23 p. 6623 - 6628

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Citation Number: 15

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 V1a/V2 receptor antagonist with favorable properties for ...