Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.
Basic Information
ID: ALA1139393
Journal: Bioorg Med Chem Lett
Title: Discovery of novel hydroxamates as highly potent tumor necrosis factor-alpha converting enzyme inhibitors. Part II: optimization of the S3' pocket.
Authors: Mazzola RD, Zhu Z, Sinning L, McKittrick B, Lavey B, Spitler J, Kozlowski J, Neng-Yang S, Zhou G, Guo Z, Orth P, Madison V, Sun J, Lundell D, Niu X.
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.
CiteXplore: 18835710
DOI: 10.1016/j.bmcl.2008.09.045
Patent ID: ┄