Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist

J Med Chem. 2006 Dec 28;49(26):7603-6. doi: 10.1021/jm0609622.

Abstract

Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzamides / administration & dosage
  • Benzamides / chemical synthesis
  • Benzamides / pharmacology*
  • Biological Availability
  • Cyclobutanes / administration & dosage
  • Cyclobutanes / chemical synthesis
  • Cyclobutanes / pharmacology*
  • Molecular Structure
  • Rats
  • Receptors, Interleukin-8A / antagonists & inhibitors*
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Receptors, Interleukin-8B / metabolism
  • Structure-Activity Relationship

Substances

  • 2-hydroxy-N,N-dimethyl-3-(2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-enylamino)benzamide
  • Benzamides
  • Cyclobutanes
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • benzamide