Synthesis and in Vitro Evaluation of Sulfonamide Isatin Michael Acceptors as Small Molecule Inhibitors of Caspase-6

详细信息    查看全文

• 作者：Wenhua Chu ; Justin Rothfuss ; Yunxiang Chu ; Dong Zhou ; Robert H. Mach
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：April 23, 2009
• 年：2009
• 卷：52
• 期：8
• 页码：2188-2191
• 全文大小：102K
• 年卷期：v.52,no.8(April 23, 2009)
• ISSN：1520-4804

文摘

A key step in the onset of Huntington’s disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments. Therefore, the inhibition of caspase-6 has been identified as a target for therapeutic drug development for the treatment of this disease. In this study, a series of isatin sulfonamide Michael acceptors having a high nanomolar potency for inhibiting caspase-6 and increased selectivity for caspase-6 versus caspase-3 inhibition is reported.