title: Synthesis and evaluation of 3-deoxy and 3-deoxy-3-fluoro derivatives of gluco- and manno-configured tetrahydropyridoimidazole glycosidase inhibitors.
abstract: Three tetrahydropyridoimidazole-type glycosidase inhibitors have been synthesized with the 3-deoxy ribo- and arabino-, and 3-deoxy-3-fluoro gluco-configurations and two of them screened for activity against α- and β-gluco- and mannosidase enzymes. Only one substance, the 3-deoxy-3-fluoro-derivative of the gluco-configured tetrahydropyridoimidazole was found to have any activity against a single enzyme, sweet almond β-glucosidase, and even then at a level 100-fold lower than that of the corresponding simple gluco-configured tetrahydropyridoimidazole thereby underlining the importance of the 3-hydroxy group in the key substrate-enzyme interactions.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Ouairy
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.forename: Bernard
authors.initials: B
authors.lastname: Delpech
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D005959:Glucosidases / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry*; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D005960:Glucosides; D007093:Imidazoles; D010940:Plant Proteins; D029701:Saccharomyces cerevisiae Proteins; C014110:4-methylumbelliferyl glucoside; D006923:Hymecromone; D005959:Glucosidases
keywords: Glycosidases; Glycosidic bond; Tetrahydroimidazopyridines; Tetrahydropyridoimidazole; Transition-state mimics