title: Synthesis of heterocyclic N-(β-D-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase.
abstract: In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylamine and propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylamine which was transformed by 1,3-dipolar cycloadditions with aromatic azides and nitrile-oxides to the corresponding O-peracetylated N-(β-D-glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides and N-(β-D-glucopyranosyl)-3-substituted-isoxazole-5-carboxamides, respectively. These compounds were O-deacetylated by Zemplén's protocol to be tested as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitors of the two series were N-(β-D-glucopyranosyl)-1-(3,5-dimethyl-phenyl)-1,2,3-triazole-4-carboxamide (K(i)=34 μM) and N-(β-D-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide (K(i)=164 μM).
authors.affiliation: Department of Organic Chemistry, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Kónya
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; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007555:Isoxazoles / Q000737:chemistry; D011817:Rabbits; D014230:Triazoles / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007555:Isoxazoles; D014230:Triazoles; D024981:Glycogen Phosphorylase