Dihydrofuro[3,4-c]pyridinones as Inhibitors of the Cytolytic Effects of the Pore-Forming Glycoprotein Perforin

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• 作者：Gersande Lena ; Joseph A. Trapani ; Vivien R. Sutton ; Annette Ciccone ; Kylie A. Browne ; Mark J. Smyth ; William A. Denny ; Julie A. Spicer
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：December 11, 2008
• 年：2008
• 卷：51
• 期：23
• 页码：7614-7624
• 全文大小：198K
• 年卷期：v.51,no.23(December 11, 2008)
• ISSN：1520-4804

文摘

Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure−activity relationships around the core bicyclic thioxofuropyridinone and pendant furan ring. This resulted in the identification of a submicromolar inhibitor of the perforin-induced lysis of Jurkat T-lymphoma cells.