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.
- bone loss
- rheumatoid arthritis
Greig, I. R., Coste, E., Ralston, S. H., & van't Hof, R. J. (2010). Discovery of biphenylketones as dual modulators of inflammation and bone loss. Bioorganic & Medicinal Chemistry Letters, 20(18), 5548-5551. https://doi.org/10.1016/j.bmcl.2010.07.055