title: Synthesis and evaluation of N-alkylated analogues of aza-galacto-fagomine - potential pharmacological chaperones for Krabbe disease.
abstract: Seven novel alkylated or acylated analogues of hexahydropyridazine aza-galacto-fagomine (AGF) was prepared and studied as glycosidase inhibitors with the aim of increasing inhibitory potency and selectivity. The enzyme galactocerebrosidase, implicated in Krabbe disease, was found to be potently inhibited by n-butyl N2-alkylated AGF.
authors.affiliation: Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark. hhj@chem.au.dk.
authors.forename: Agnete H
authors.initials: AH
authors.lastname: Viuff
authors.forename: Henrik H
authors.initials: HH
authors.lastname: Jensen
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005698:Galactosylceramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050112:Imino Pyranoses / Q000737:chemistry / Q000494:pharmacology*; D007965:Leukodystrophy, Globoid Cell / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D011724:Pyridazines; C105643:fagomine; D005698:Galactosylceramidase