Discovery of biphenylketones as dual modulators of inflammation and bone loss

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5548-51. doi: 10.1016/j.bmcl.2010.07.055. Epub 2010 Jul 18.

Abstract

Biphenylketones were identified as novel inhibitors of NFkappaB activation. Structure-activity studies led to the identification of compound 4c, which had good potency against osteoclasts (IC50=0.8 microM), showed oral activity, and was able to completely prevent inflammation and bone loss in vivo.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis / chemically induced
  • Arthritis / drug therapy*
  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / pharmacology
  • Benzene Derivatives / therapeutic use*
  • Cell Line
  • Cell Survival / drug effects
  • Female
  • Inflammation / drug therapy
  • Ketones / chemistry*
  • Ketones / pharmacology
  • Ketones / therapeutic use*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • NF-kappa B / immunology
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • Osteoporosis / drug therapy*
  • Polycyclic Aromatic Hydrocarbons / chemistry
  • Polycyclic Aromatic Hydrocarbons / pharmacology
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Benzene Derivatives
  • Ketones
  • NF-kappa B
  • Polycyclic Aromatic Hydrocarbons
  • Tumor Necrosis Factor-alpha