Structural–activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production

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• 作者：Daljinder K. Kahlon ; Theresa A. Lansdell ; Jason S. Fisk ; Jetze J. Tepe
• 关键词：NF-kappaB ; IL-6 ; Imidazolines ; Inflammation
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：15 April 2009
• 年：2009
• 卷：17
• 期：8
• 页码：3093-3103
• 全文大小：504 K

文摘

We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-κB inhibitors. The structure–activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-κB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-κB reporter assays with inhibition of IL-6 production in IL-1β stimulated human blood. Several derivatives were found to inhibit NF-κB mediated IL-6 production in the nanomolar range in IL-1β stimulated human blood.