Development of triarylsulfonamides as novel anti-inflammatory agents

Iain R. Greig, Coste Emmanuel, Stuart Ralston, Robert van 't Hof

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)816-820
Number of pages5
JournalBioorganic & Medicinal Chemistry Letters
Volume23
Issue number3
Early online date27 Dec 2012
DOIs
Publication statusPublished - Feb 2013

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Anti-Inflammatory Agents
Inflammation
ABD455
In Vitro Techniques

Keywords

  • TNF-a
  • NFκB
  • inflammation
  • rheumatoid arthritis
  • bone loss

Cite this

Development of triarylsulfonamides as novel anti-inflammatory agents. / Greig, Iain R.; Emmanuel, Coste; Ralston, Stuart; van 't Hof, Robert.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 23, No. 3, 02.2013, p. 816-820.

Research output: Contribution to journalArticle

Greig, Iain R. ; Emmanuel, Coste ; Ralston, Stuart ; van 't Hof, Robert. / Development of triarylsulfonamides as novel anti-inflammatory agents. In: Bioorganic & Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 3. pp. 816-820.
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