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Development of triarylsulfonamides as novel anti-inflammatory agents
Iain R Greig1, Emmanuel Coste, Stuart H Ralston
1Kosterlitz Centre for Therapeutics, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. i.greig@abdn.ac.uk
Abstract:
Triaylsulfonamides were identified as novel anti-inflammatory agents, acting by inhibition of RANKL and TNFα 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 (IC(50) >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.
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