Inhibition of Tpl2 kinase and TNFα production with quinoline-3-carbonitriles for the treatment of rheumatoid arthritis
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- 作者：Yonghan Hu ; Neal Green ; Lori K. Gavrin ; Kristin Janz ; Neelu Kaila ; Huan-Qiu Li ; Jennifer R. Thomason ; John W. Cuozzo ; J. Perry Hall ; Sang Hsu ; et al.
- 关键词：Tpl2 kinase ; Quinoline-3-carbonitrile
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2006
- 出版时间：1 December 2006
- 年：2006
- 卷：16
- 期：23
- 页码：6067-6072
- 全文大小：188 K
文摘
The synthesis and structure–activity studies of a series of quinoline-3-carbonitriles as inhibitors of Tpl2 kinase are described. Potent inhibitors of Tpl2 kinase with selectivity against a panel of selected kinases in enzymatic assays and specificity in cell-based phosphorylation assays in LPS-treated human monocytes were identified. Selected inhibitors with moderate activity in human whole blood assay effectively inhibited LPS/D-Gal induced TNFα release when administered intraperitoneally in mice.