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Basic Information

ID: ALA1141560

Journal: Bioorg Med Chem Lett

Title: Alpha,beta-cyclic-beta-benzamido hydroxamic acids: novel templates for the design, synthesis, and evaluation of selective inhibitors of TNF-alpha converting enzyme (TACE).

Authors: Ott GR, Asakawa N, Lu Z, Liu RQ, Covington MB, Vaddi K, Qian M, Newton RC, Christ DD, Traskos JM, Decicco CP, Duan JJ.

Abstract: Selective inhibitors of TNF-alpha Converting Enzyme (TACE) based on (1R,2S)-cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl beta-benzamido hydroxamic acids have been synthesized and evaluated. This study has led to the discovery of novel inhibitors whose profiles include activity against TACE in an enzyme assay, potency in the suppression of LPS-stimulated TNF-alpha in human whole blood, selectivity against a panel of MMPs and oral bioavailability.

CiteXplore: 18061445

DOI: 10.1016/j.bmcl.2007.11.059