title: Synthesis of C-5a-substituted derivatives of 4-epi-isofagomine: notable β-galactosidase inhibitors and activity promotors of GM1-gangliosidosis related human lysosomal β-galactosidase mutant R201C.
abstract: From an easily available partially protected analog of 1-deoxy-L-gulo-nojirimycin, by chain-branching at C-4 and suitable modification, lipophilic analogs of the powerful β-D-galactosidase inhibitor 4-epi-isofagomine have been prepared. New compounds exhibit considerably improved inhibitory activities when compared with the unsubstituted parent compound and may serve as leads toward new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease.
authors.affiliation: Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Thonhofer
authors.affiliation: Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weber
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: Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Christina
authors.initials: C
authors.lastname: Tysoe
authors.affiliation: Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Department of Pediatrics, Laboratory of Metabolic Diseases, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Pabst
authors.affiliation: Department of Pediatrics, Laboratory of Metabolic Diseases, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria.
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
authors.affiliation: Glycogroup, Institute of 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 of 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: Department of Pediatrics, Laboratory of Metabolic Diseases, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Tschernutter
authors.affiliation: Department of Pediatrics, Laboratory of Metabolic Diseases, MedUni Graz, Auenbruggerplatz 30, A-8036 Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Windischhofer
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: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000737:chemistry; D016537:Gangliosidosis, GM1 / Q000188:drug therapy; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D050112:Imino Pyranoses / Q000138:chemical synthesis* / Q000737:chemistry; D009085:Mucopolysaccharidosis IV / Q000188:drug therapy; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C470465:1-deoxy-gulonojirimycin; D050112:Imino Pyranoses; C098432:isofagomine; D017485:1-Deoxynojirimycin; D001616:beta-Galactosidase
keywords: 4-Epi-isofagomine; G(M1)-gangliosidosis; Galactosidase inhibitor; Iminoalditol; Pharmacological chaperone