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Basic Information

ID: ALA1153078

Journal: Bioorg Med Chem

Title: Design and synthesis of acetamido tri- and tetra-hydroxyazepanes: potent and selective beta-N-acetylhexosaminidase inhibitors.

Authors: Li H, Marcelo F, Bello C, Vogel P, Butters TD, Rauter AP, Zhang Y, Sollogoub M, Blériot Y.

Abstract: A series of seven-membered iminosugars bearing an acetamido group beta- or gamma- to the endocyclic nitrogen have been synthesized via simple transformations of previously described polysubstituted azepanes. These tetra- and trihydroxylated acetamido azepanes are ring homologues of 2-acetamido-1,2-dideoxy-glyconojirimycins and 2-acetamido-1-N-iminosugars respectively. Screening of these azepanes towards a range of commercially available glycosidases demonstrated their potential as selective and potent hexosaminidase inhibitors with K(i)'s in the submicromolar range. A correlation between the relative configuration of the azepanes and their ability to inactivate hexosaminidases was also observed for the first time for this class of compounds with one notable exception for the most potent compound.

CiteXplore: 19592259

DOI: 10.1016/j.bmc.2009.06.022