Discovery of biphenylketones as dual modulators of inflammation and bone loss

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Greig, Iain R.¹  Coste, Emmanuel²  Ralston, Stuart H.²  van't Hof, Rob J.² 

[1] Univ Aberdeen, Sch Med Sci, Inst Med Sci, Aberdeen AB25 2ZD, Scotland

[2] Univ Edinburgh, Mol Med Ctr, Rheumat Dis Unit, Edinburgh EH4 2XU, Midlothian, Scotland

关键词: Inflammation;    Bone loss;    Rheumatoid arthritis;    TNF alpha;    NF kappa B;    RANKL;   

DOI  :  10.1016/j.bmcl.2010.07.055

来源: Elsevier

【 摘 要 】

Biphenylketones were identified as novel inhibitors of NF kappa B activation. Structure-activity studies led to the identification of compound 4c, which had good potency against osteoclasts (IC(50) = 0.8 mu M), showed oral activity, and was able to completely prevent inflammation and bone loss in vivo. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

Free