α,β-Cyclic-β-benzamido hydroxamic acids: Novel templates for the design, synthesis, and evaluation of selective inhibitors of TNF-α converting enzyme (TACE)

Selective inhibitors of TNF-α Converting Enzyme (TACE) based on (1R,2S)-cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl β-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-α in human whole blood, selectivity against a panel of MMPs and oral bioavailability.

Graphical abstractSelective inhibitors of TNF-α Converting Enzyme (TACE) based on novel α,β-cyclic-β-benzamido hydroxamic acids have been synthesized and evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide