Discovery of a novel, potent and orally active series of γ-lactams as selective NK1 antagonists

Sunil Paliwal, Gregory A. Reichard, Sapna Shah, Michelle Laci Wrobleski, Cheng Wang, Carmine Stengone, Hon Chung Tsui, Dong Xiao, Ruth A. Duffy, Jean E. Lachowicz, Amin A. Nomeir, Geoffrey B. Varty, Neng Yang Shih

Research output: Contribution to journalArticlepeer-review

Abstract

Strategic replacement of the nitrogen of the lead compound 1 in the original cyclic urea series with a carbon resulted in the discovery of a novel, potent and orally more efficacious γ-lactam series of selective NK1 antagonists. Optimization of the lactam series culminated in the identification of compounds with high binding affinity and excellent oral CNS activity.

Original languageEnglish
Pages (from-to)4168-4171
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number14
DOIs
StatePublished - Jul 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Keywords

  • CNS
  • Emesis
  • Lactam
  • NK1
  • Substance P

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