Highly potent inhibitors of TNF-alpha production. Part I: discovery of new chemical leads and their structure-activity relationships

Bioorg Med Chem. 2002 Dec;10(12):3757-86. doi: 10.1016/s0968-0896(02)00381-4.

Abstract

Discovery of new chemical leads of inhibitors for TNF-alpha production starting from the chemical modification of 1 is reported. Further biological studies of 1 to disclose the site of its action strongly suggested that 1 inhibits LPS-induced TNF-alpha expression in the liver and spleen of mice. Structure-activity relationships (SARs) are also discussed and full details including the chemistry are reported.

MeSH terms

  • Animals
  • Female
  • Indans / administration & dosage
  • Indans / chemical synthesis*
  • Indans / pharmacology
  • Inhibitory Concentration 50
  • Injections, Intravenous
  • Lipopolysaccharides / pharmacology
  • Liver / chemistry
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organophosphorus Compounds / administration & dosage
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / pharmacology
  • Spleen / chemistry
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Indans
  • Lipopolysaccharides
  • Organophosphorus Compounds
  • Tumor Necrosis Factor-alpha