Small-Molecule Inhibitors of Cytokine-Mediated STAT1 Signal Transduction in 尾-Cells with Improved Aqueous Solubility

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• 作者：Stephen S. Scully ; Alicia J. Tang ; Morten Lundh ; Carrie M. Mosher ; Kedar M. Perkins ; Bridget K. Wagner
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：May 23, 2013
• 年：2013
• 卷：56
• 期：10
• 页码：4125-4129
• 全文大小：301K
• 年卷期：v.56,no.10(May 23, 2013)
• ISSN：1520-4804

文摘

We previously reported the discovery of BRD0476 (1), a small molecule generated by diversity-oriented synthesis that suppresses cytokine-induced 尾-cell apoptosis. Herein, we report the synthesis and biological evaluation of 1 and analogues with improved aqueous solubility. By replacing naphthyl with quinoline moieties, we prepared active analogues with up to a 1400-fold increase in solubility from 1. In addition, we demonstrated that 1 and analogues inhibit STAT1 signal transduction induced by IFN-纬.