含有迈克尔加成受体的异吲哚酮磺酰胺类似物：一类新型的半胱天冬酶3/7抑制剂。
Isatin sulfonamide analogs containing a Michael addition acceptor: a new class of caspase 3/7 inhibitors.
作者信息
Chu Wenhua, Rothfuss Justin, d'Avignon André, Zeng Chenbo, Zhou Dong, Hotchkiss Richard S, Mach Robert H
机构信息
Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110, USA.
出版信息
J Med Chem. 2007 Jul 26;50(15):3751-5. doi: 10.1021/jm070506t. Epub 2007 Jun 23.
A series of isatin sulfonamide analogs having a Michael acceptor were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated. These compounds have nanomolar potency for inhibiting the 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 between 11d and benzylmercaptan as a model for Cys-285 in the active site of caspase-3.
制备了一系列具有迈克尔受体的异吲哚啉酮磺酰胺类似物，并评估了它们对胱天蛋白酶-1、-3、-6、-7和-8的抑制活性。这些化合物对执行性胱天蛋白酶（胱天蛋白酶-3和胱天蛋白酶-7）具有纳摩尔级的抑制活性，而对胱天蛋白酶-1、胱天蛋白酶-6和胱天蛋白酶-8的抑制活性较低。通过对11d与苄硫醇之间反应的核磁共振研究，以胱天蛋白酶-3活性位点中的半胱氨酸-285为模型，研究了抑制机制。
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