title: C-Glucopyranosyl-1,2,4-triazol-5-ones: synthesis and inhibition of glycogen phosphorylase.
abstract: Various C-glucopyranosyl-1,2,4-triazolones were designed as potential inhibitors of glycogen phosphorylase. Syntheses of these compounds were performed with O-perbenzoylated glucose derivatives as precursors. High temperature ring closure of N(1)-carbamoyl-C-β-D-glucopyranosyl formamidrazone gave 3-β-D-glucopyranosyl-1,2,4-triazol-5-one. Reaction of N(1)-tosyl-C-β-D-glucopyranosyl formamidrazone with ClCOOEt furnished 3-β-D-glucopyranosyl-1-tosyl-1,2,4-triazol-5-one. In situ prepared β-D-glucopyranosylcarbonyl isocyanate was transformed by PhNHNHBoc into 3-β-D-glucopyranosyl-1-phenyl-1,2,4-triazol-5-one, while the analogous 1-(2-naphthyl) derivative was obtained from the unsubstituted triazolone by naphthalene-2-boronic acid in a Cu(II) catalyzed N-arylation. Test compounds were prepared by Zemplén deacylation. The new glucose derivatives had weak or no inhibition of rabbit muscle glycogen phosphorylase b: the best inhibitor was 3-β-D-glucopyranosyl-1-(2-naphthyl)-1,2,4-triazol-5-one (Ki = 80 µM).
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Bokor
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Széles
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.affiliation: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary. Electronic address: somsak@tigris.unideb.hu.
authors.forename: László
authors.initials: L
authors.lastname: Somsák
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000737:chemistry; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D007700:Kinetics; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology; D009281:Naphthalenes / Q000737:chemistry; D011817:Rabbits; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001897:Boronic Acids; D004791:Enzyme Inhibitors; D005960:Glucosides; D009281:Naphthalenes; D014230:Triazoles; D024981:Glycogen Phosphorylase; D005947:Glucose
keywords: 1,2,4-Triazol-5-one; C-glucosyl derivative; Glycogen phosphorylase; Inhibitor