Discovery of novel hydroxamates as highly potent tumor necrosis factor-α converting enzyme inhibitors. Part II: Optimization of the S3′ pocket
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- 作者：Robert D. Mazzola Jr. ; Zhaoning Zhu ; Lisa Sinning ; Brian McKittrick ; Brian Lavey ; James Spitler ; Joseph Kozlowski ; Shih Neng-Yang ; Guowei Zhou ; Zhuyan Guo ; Peter Orth ; Vincent Madison ; Jing Sun ; Danie
- 关键词：TACE inhibitors ; MMP inhibitors
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：1 November 2008
- 年：2008
- 卷：18
- 期：21
- 页码：5809-5814
- 全文大小：247 K
文摘
A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1′–S3′ pocket.