title: Synthesis of C-xylopyranosyl- and xylopyranosylidene-spiro-heterocycles as potential inhibitors of glycogen phosphorylase.
abstract: New derivatives of d-xylose with aglycons of the most efficient glucose derived inhibitors of glycogen phosphorylase were synthesized to explore the specificity of the enzyme towards the structure of the sugar part of the molecules. Thus, 2-(β-d-xylopyranosyl)benzimidazole and 3-substituted-5-(β-d-xylopyranosyl)-1,2,4-triazoles were obtained in multistep procedures from O-perbenzoylated β-d-xylopyranosyl cyanide. Cycloadditions of nitrile-oxides and O-peracetylated exo-xylal obtained from the corresponding β-d-xylopyranosyl cyanide furnished xylopyranosylidene-spiro-isoxazoline derivatives. Oxidative ring closure of O-peracetylated β-d-xylopyranosyl-thiohydroximates prepared from 1-thio-β-d-xylopyranose and nitrile-oxides gave xylopyranosylidene-spiro-oxathiazoles. The fully deprotected test compounds were assayed against rabbit muscle glycogen phosphorylase b to show moderate inhibition for 3-(2-naphthyl)-5-(β-d-xylopyranosyl)-1,2,4-triazole (IC50=0.9mM) only.
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary. Electronic address: somsak.laszlo@science.unideb.hu.
authors: László
authors: L
authors: Somsák
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Éva
authors: É
authors: Bokor
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Beáta
authors: B
authors: Czibere
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Katalin
authors: K
authors: Czifrák
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Csenge
authors: C
authors: Koppány
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: László
authors: L
authors: Kulcsár
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Sándor
authors: S
authors: Kun
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Enikő
authors: E
authors: Szilágyi
authors: Department of Organic Chemistry, University of Debrecen, POB 20, H-4010 Debrecen, Hungary.
authors: Marietta
authors: M
authors: Tóth
authors: Department of Medical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors: Tibor
authors: T
authors: Docsa
authors: Department of Medical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
authors: Pál
authors: P
authors: Gergely
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000201:enzymology*; D011817:Rabbits; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014994:Xylose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D013141:Spiro Compounds; C431715:xylopyranose; D014994:Xylose; D024982:Glycogen Phosphorylase, Muscle Form
keywords: 1,2,4-Triazole; Benzimidazole; Glycogen phosphorylase inhibitor; Spiro-1,4,2-oxathiazole; Spiro-isoxazoline; Xylose derivative