Next-generation spirobenzazepines: identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies.
Min Amy Xiang, 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
Research and Early Development, Johnson & Johnson Pharmaceutical Research & Development, 8 Clarke Drive, Cranbury, NJ 08512, USA.
Bioorganic & medicinal chemistry letters 2007 Dec 1We 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.
Citation
Min Amy Xiang, 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. Next-generation spirobenzazepines: identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies. Bioorganic & medicinal chemistry letters. 2007 Dec 1;17(23):6623-8
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PMID: 17942308
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