Triaylsulfonamides were identified as novel anti-inflammatory agents, acting by inhibition of RANKL and TNFa signaling. Structure-activity studies led to the identification of compounds with in vitro potencies of < 100 nM against J774 macrophages and osteoclasts, but with little activity against osteoblasts or hepatocytes (IC50 > 50 µM). A representative compound (4k, ABD455) was able to completely prevent inflammation in vivo in a prevention model and was highly effective at controlling inflammation in a treatment model.
- rheumatoid arthritis
- bone loss
Greig, I. R., Emmanuel, C., Ralston, S., & van 't Hof, R. (2013). Development of triarylsulfonamides as novel anti-inflammatory agents. Bioorganic & Medicinal Chemistry Letters, 23(3), 816-820. https://doi.org/10.1016/j.bmcl.2012.11.067