Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373029 | Bioorganic & Medicinal Chemistry Letters | 2008 | 5 Pages |
Abstract
Two novel oxaspiro[4.4]nonane β-benzamido hydroxamic scaffolds have been synthesized in enantio- and diasteriomerically pure form. These templates proved to be exceptional platforms that have led to the discovery of potent inhibitors of TACE that are active in a cellular assay measuring suppression of LPS-induced TNF-α. Furthermore, these inhibitors are selective against related MMPs, demonstrate permeability in a Caco-2 assay, and display good oral bioavailability.
Graphical abstractSelective inhibitors of TNF-α Converting Enzyme (TACE) based on novel oxaspiro[4.4]nonane β-benzamido hydroxamic scaffolds acids have been synthesized and evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Gregory R. Ott, Naoyuki Asakawa, Rui-Qin Liu, Maryanne B. Covington, Mingxin Qian, Krishna Vaddi, Robert C. Newton, James M. Trzaskos, David D. Christ, Laurine Galya, Thomas Scholz, Will Marshall, James J.-W. Duan,