Discovery and structure-activity relationships of 6-(benzoylamino)benzoxaboroles as orally active anti-inflammatory agents

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• 作者：Tsutomu Akama ; Chen Dong ; Charlotte Virtucio ; Yvonne R. Freund ; Daitao Chen ; Matthew D. Orr ; Robert T. Jacobs ; Yong-Kang Zhang ; Vincent Hern ; ez ; Yang Liu ; Anne Wu ; Wei Bu ; Liang Liu ; Kurt Jarnagin ; Jacob J. Plattner
• 关键词：Benzoxaborole ; Structure&ndash ; activity relationships ; Anti-inflammatory ; Cytokine ; Tumor necrosis factor-alpha ; Interleukin-1beta ; Interleukin-6 ; Pharmacokinetics ; Collagen-induced arthritis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 November, 2013
• 年：2013
• 卷：23
• 期：21
• 页码：5870-5873
• 全文大小：625 K

文摘

Structure-activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-¦Á, IL-1¦Â, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC₅₀ values between 0.19 and 0.50 ¦ÌM, inhibited LPS-induced TNF-¦Á and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile.