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ID: ALA1136542
Journal: Bioorg Med Chem Lett
Title: Discovery of N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamides as potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
Authors: Duan JJ, Lu Z, Xue CB, He X, Seng JL, Roderick JJ, Wasserman ZR, Liu RQ, Covington MB, Magolda RL, Newton RC, Trzaskos JM, Decicco CP.
Abstract: New inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered using an N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamide scaffold. The series was found to be potent in a porcine TACE (pTACE) assay with IC(50)s typically below 5 nM. For most compounds, selectivity for pTACE relative to MMP-1,-2, and -9 is at least 300-fold. Compound 2o was potent in inhibition of TNFalpha production in a human whole blood assay (WBA) with an IC(50) of 0.42 micro M.
CiteXplore: 12781190