Synthesis of N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase

Katalin Czifrák; Zsuzsa Hadady; Tibor Docsa; Pál Gergely; Jürgen Schmidt; Ludger Wessjohann; László Somsák

doi:10.1016/j.carres.2006.03.002

Synthesis of N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids as potential inhibitors of glycogen phosphorylase

Carbohydr Res. 2006 Jun 12;341(8):947-56. doi: 10.1016/j.carres.2006.03.002. Epub 2006 Mar 29.

Authors

Katalin Czifrák¹, Zsuzsa Hadady, Tibor Docsa, Pál Gergely, Jürgen Schmidt, Ludger Wessjohann, László Somsák

Affiliation

¹ Department of Organic Chemistry, Faculty of Science, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.

PMID: 16564511
DOI: 10.1016/j.carres.2006.03.002

Abstract

O-peracetylated N-(beta-D-glucopyranosyl)imino trimethylphosphorane obtained in situ from 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl azide and PMe3 was reacted with saturated and unsaturated aliphatic and aromatic dicarboxylic acids, or their anhydrides, or monoesters to give the corresponding N-(beta-D-glucopyranosyl) monoamides of dicarboxylic acids or derivatives. The acetyl protecting groups were removed according to the Zemplén protocol to give a series of compounds which showed moderate inhibitory effects against rabbit muscle glycogen phosphorylase b. The best inhibitor was 3-(N-beta-D-glucopyranosyl-carbamoyl)propanoic acid (7) with Ki = 20 microM.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis*
Amides / pharmacology
Animals
Dicarboxylic Acids / chemistry*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Glycogen Phosphorylase, Muscle Form / antagonists & inhibitors*
Glycogen Phosphorylase, Muscle Form / metabolism
Hydrogen Bonding
Kinetics
Molecular Structure
Rabbits

Substances

Amides
Dicarboxylic Acids
Enzyme Inhibitors
Glycogen Phosphorylase, Muscle Form