title: Synthesis of 2-(β-D-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles for inhibition of glycogen phosphorylase.
abstract: Aromatic aldehyde 4-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)semicarbazones were synthesized by the addition of different hydrazones onto O-peracetylated β-d-glucopyranosyl isocyanate. Oxidative transformations of these precursors gave O-protected 2-(β-d-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles. Removal of the O-acetyl protecting groups under Zemplén conditions gave test compounds to show low micromolar inhibition against rabbit muscle glycogen phosphorylase b. Best inhibitors of these series were 4-(β-d-glucopyranosyl)semicarbazones of 4-nitrobenzaldehyde (Ki=4.5μM), 2-naphthaldehyde (Ki=5.5μM) and 2-(β-d-glucopyranosylamino)-5-(4-methylphenyl)-1,3,4-oxadiazole (Ki=12μM).
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary. Electronic address: toth.marietta@science.unideb.hu.
authors.forename: Marietta
authors.initials: M
authors.lastname: Tóth
authors.forename: Béla
authors.initials: B
authors.lastname: Szőcs
authors.forename: Tímea
authors.initials: T
authors.lastname: Kaszás
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
chemical_list: D004791:Enzyme Inhibitors; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole; D024982:Glycogen Phosphorylase, Muscle Form
keywords: 1,3,4-Oxadiazole; Glycogen phosphorylase; Inhibitor; Semicarbazone; β-d-Glucopyranosyl derivatives