Synthesis of 2-(β-D-glucopyranosylamino)-5-substituted-1,3,4-oxadiazoles for inhibition of glycogen phosphorylase

Carbohydr Res. 2013 Nov 15:381:196-204. doi: 10.1016/j.carres.2013.04.025. Epub 2013 Apr 27.

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).

Keywords: 1,3,4-Oxadiazole; Glycogen phosphorylase; Inhibitor; Semicarbazone; β-d-Glucopyranosyl derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Phosphorylase, Muscle Form / antagonists & inhibitors*
  • Glycogen Phosphorylase, Muscle Form / metabolism
  • Molecular Structure
  • Muscle, Skeletal / enzymology*
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Rabbits
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Oxadiazoles
  • 1,3,4-oxadiazole
  • Glycogen Phosphorylase, Muscle Form