title: Synthesis of 2-(β-D-glucopyranosyl)-5-(substituted-amino)-1,3,4-oxa- and -thiadiazoles for the inhibition of glycogen phosphorylase.
abstract: O-Perbenzoylated 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone was prepared in the reaction of O-perbenzoylated β-d-glucopyranosyl cyanide and 4-phenylsemicarbazide in the presence of Raney-Ni. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone furnished the corresponding 4-acyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazones. The reaction of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde semicarbazone with the corresponding thiosemicarbazide resulted in O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone and its 4-phenyl derivative. Acylation of O-perbenzoylated C-(β-d-glucopyranosyl)formaldehyde thiosemicarbazone provided the corresponding 4-acyl-2-acylamino-5-(β-d-glucopyranosyl)-Δ(2)-1,3,4-thiadiazolidines. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosyl)-5-substituted-amino-1,3,4-oxa- and -thiadiazoles. The O-benzoyl protecting groups were removed under base-catalysed transesterification conditions. The C-glucopyranosyl heterocyclic compounds proved inactive against rabbit muscle glycogen phosphorylase b, however, the semicarbazones showed moderate inhibition (best inhibitor was 4-phenyl-[C-(β-d-glucopyranosyl)formaldehyde]semicarbazone (Ki=29μM).
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Szőcs
authors.forename: Marietta
authors.initials: M
authors.lastname: Tóth
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.forename: László
authors.initials: L
authors.lastname: Somsák
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000201:enzymology*; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; C583463:1,3,4-oxadiazole; D024982:Glycogen Phosphorylase, Muscle Form
keywords: C-Glycosyl-1,3,4-oxadiazole; C-Glycosyl-1,3,4-thiadiazole; C-Glycosyl-formaldehyde (thio)semicarbazone; Glycogen phosphorylase; Inhibitor