Isatin Sulfonamide Analogs Containing a Michael Addition Acceptor: A New Class of Caspase 3/7 Inhibitors
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- 作者：Wenhua Chu ; Justin Rothfuss ; André ; d'Avignon ; Chenbo Zeng ; Dong Zhou ; Richard S. Hotchkiss ; Robert H. Mach
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：July 26, 2007
- 年：2007
- 卷：50
- 期：15
- 页码：3751 - 3755
- 全文大小：68K
- 年卷期：v.50,no.15(July 26, 2007)
- ISSN：1520-4804
文摘
A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies forinhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibitingthe executioner caspases, caspase-3 and caspase-7, and have a low potency for inhibiting caspase-1, caspase-6, and caspase-8. The inhibition mechanism was investigated through NMR studies of the reaction between11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.