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ID: ALA1141492

Journal: Bioorg Med Chem Lett

Title: Potent, exceptionally selective, orally bioavailable inhibitors of TNF-alpha Converting Enzyme (TACE): novel 2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamide P1' substituents.

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

Abstract: Novel ((2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamides were found to be excellent P1' substituents in conjunction with unique constrained beta-amino hydroxamic acid scaffolds for the discovery of potent selective inhibitors of TNF-alpha Converting Enzyme (TACE). Optimized examples proved potent for TACE, exceptionally selective over a wide panel of MMP and ADAM proteases, potent in the suppression of LPS-induced TNF-alpha in human whole blood and orally bioavailable.

CiteXplore: 18242982

DOI: 10.1016/j.bmcl.2008.01.075