Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-α converting enzyme (TACE)

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• 作者：James E. Sheppeck II ; John L. Gilmore ; Anle Yang ; Xiao-Tao Chen ; Chu-Biao Xue ; John Roderick ; Rui-Qin Liu ; Maryanne B. Covington ; Carl P. Decicco ; James J.-W. Duan
• 关键词：TACE ; TACE inhibitor ; Non-hydroxamate ; MMP ; Matrix metalloprotease ; Matrix metalloproteinase ; TNF
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 March 2007
• 年：2007
• 卷：17
• 期：5
• 页码：1413-1417
• 全文大小：180 K

文摘

A series of novel hydantoins was designed and synthesized as structural alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted hydantoins exhibited activity with IC₅₀ values of 11–60 nM against porcine TACE in vitro and excellent selectivity against other MMPs.