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.
Iain R Greig  1 ,  Emmanuel Coste ,  Stuart H Ralston ,  Rob J van't Hof
Affiliations
  • 1. School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom. [email protected]
PMID: 20692834 DOI: 10.1016/j.bmcl.2010.07.055
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.