title: 5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease.
abstract: Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-D-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.
authors.affiliation: Glycogroup, Institute for Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Thonhofer
authors.affiliation: Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Andres
authors.initials: A
authors.lastname: Gonzalez Santana
authors.affiliation: Institute for Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Institute for Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Torvisco Gomez
authors.affiliation: Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Saf
authors.affiliation: Glycogroup, Institute for Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schalli
authors.affiliation: Glycogroup, Institute for Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. Electronic address: stuetz@tugraz.at.
authors.forename: Arnold E
authors.initials: AE
authors.lastname: Stütz
authors.affiliation: Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000795:Fabry Disease / Q000188:drug therapy / Q000201:enzymology; D005696:Galactosidases / Q000037:antagonists & inhibitors*; D016537:Gangliosidosis, GM1 / Q000188:drug therapy / Q000201:enzymology; D054879:Halogenation; D006801:Humans; D050112:Imino Pyranoses / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; C098432:isofagomine; D005696:Galactosidases
keywords: Fabry's disease; Fluorosugar; G(M1)-gangliosidosis; Galactosidase inhibitor; Iminoalditol; Pharmacological chaperone