Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-alpha converting enzyme (TACE) inhibitors.
Basic Information
ID: ALA1137760
Journal: Bioorg Med Chem
Title: Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-alpha converting enzyme (TACE) inhibitors.
Authors: Park K, Gopalsamy A, Aplasca A, Ellingboe JW, Xu W, Zhang Y, Levin JI.
Abstract: A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1' moiety was identified as inhibitors of TNF-alpha converting enzyme (TACE). The structure-activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds investigated, 2-(4-(but-2-ynyloxy)phenylsulfonamido)-3-(1-(4-methoxybenzyl)-1H-indol-3-yl)propanoic acid (12p) has the best in vitro potency against isolated TACE enzyme with an IC(50) of 80 nM. Compound 12p also shows good selectivity over MMP-1, -13, -14.
CiteXplore: 19410464
DOI: 10.1016/j.bmc.2009.04.033
Patent ID: ┄