title: Development of triarylsulfonamides as novel anti-inflammatory agents.
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.
authors.affiliation: Kosterlitz Centre for Therapeutics, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. i.greig@abdn.ac.uk
authors.forename: Iain R
authors.initials: IR
authors.lastname: Greig
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coste
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van 't Hof
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D006801:Humans; D015394:Molecular Structure; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C581848:ABD455; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D053245:RANK Ligand; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha