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ID: ALA1140572

Journal: Bioorg Med Chem Lett

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

Authors: Xiang MA, Rybczynski PJ, Patel M, Chen RH, McComsey DF, Zhang HC, Gunnet JW, Look R, Wang Y, Minor LK, Zhong HM, Villani FJ, Demarest KT, Damiano BP, Maryanoff BE.

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.

CiteXplore: 17942308

DOI: 10.1016/j.bmcl.2007.09.059