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

  • Bioorg Med Chem Lett. 2007 Dec 1;17(23):6623-8. doi: 10.1016/j.bmcl.2007.09.059.
Min Amy Xiang  1 ,  Philip J Rybczynski ,  Mona Patel ,  Robert H Chen ,  David F McComsey ,  Han-Cheng Zhang ,  Joseph W Gunnet ,  Richard Look ,  Yuanping Wang ,  Lisa K Minor ,  H Marlon Zhong ,  Frank J Villani ,  Keith T Demarest ,  Bruce P Damiano ,  Bruce E Maryanoff
Affiliations
  • 1. Research and Early Development, Johnson & Johnson Pharmaceutical Research & Development, 8 Clarke Drive, Cranbury, NJ 08512, USA.
PMID: 17942308 DOI: 10.1016/j.bmcl.2007.09.059
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.