Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4 receptor with anti-cachectic activity

Joe A. Tran, Fabio C. Tucci, Wanlong Jiang, Dragan Marinkovic, Caroline W. Chen, Melissa Arellano, Stacy Markison, Beth A. Fleck, Jenny Wen, Nicole S. White, Joseph Pontillo, John Saunders, Daniel Marks, Sam R. Hoare, Ajay Madan, Alan C. Foster, Chen Chen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

A series of pyrrolidinones derived from phenylalanines were synthesized as potent antagonists of the human melanocortin-4 receptor. These compounds showed high potencies and selectivities, and several of them had good oral bioavailabilities. In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.

Original languageEnglish (US)
Pages (from-to)5166-5176
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2007

Keywords

  • Animal model
  • Antagonist
  • Cachexia
  • Melanocortin-4 receptor
  • Pharmacokinetics
  • Pyrrolidinone
  • Synthesis

ASJC Scopus subject areas

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

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