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ID: ALA1133837

Journal: Bioorg Med Chem Lett

Title: Discovery of selective hydroxamic acid inhibitors of tumor necrosis factor-alpha converting enzyme.

Authors: Holms J, Mast K, Marcotte P, Elmore I, Li J, Pease L, Glaser K, Morgan D, Michaelides M, Davidsen S.

Abstract: Modification of the P(1)' substituent of macrocyclic matrix metalloproteinase (MMP) inhibitors provided compounds that are selective for inhibition of tumor necrosis factor-alpha converting enzyme (TACE) over MMP-1 and MMP-2. Several analogues potently inhibited the release of TNF-alpha in a THP-1 cellular assay. Compounds containing a trimethoxyphenyl group in the P(1)' substituent demonstrated TACE selectivity across several series of hydroxamate-based inhibitors.

CiteXplore: 11677124

DOI: 10.1016/s0960-894x(01)00603-5