Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1375005 | Bioorganic & Medicinal Chemistry Letters | 2008 | 6 Pages |
Abstract
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.
Graphical abstractWe herein disclose a novel series of cyclopropyl hydroxamates that are potent and selective TACE inhibitors with Ki values in the picomolar range.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
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, Daniel Lundell, Xiaoda Niu,