Synthesis of 4-amidomethyl-1-glucosyl-1,2,3-triazoles and evaluation as glycogen phosphorylase inhibitors

David Goyard, Tibor Docsa, Pál Gergely, Jean Pierre Praly, Sébastien Vidal

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18 Citations (Scopus)

Abstract

Glycogen phosphorylase (GP) appears as a key enzyme for the control of hyperglycemia in the context of type 2 diabetes. In order to gain additional data for structure-activity studies of the inhibition of this enzyme, a series of eight GP inhibitor candidates were prepared from peracetylglucopyranosyl azide 1 by click-chemistry. The need for a N-Boc-protected propargylamine was identified in the CuAAC with azide 1 under Meldal's conditions, while Sharpless' conditions were better adapted to the CuAAC of azide 1 with propargyl bromide. Cycloaddition of Boc-propargylamine with azide 1 afforded the N-Boc precursor of a 4-aminomethyl-1-glucosyl-1,2,3-triazole which gave access to a series of eight amide and sulfonamide derivatives. After deacetylation, enzymatic studies revealed poor to moderate inhibitions toward this enzyme. The N-Boc-protected amine was the best inhibitor (IC50 = 620 μM) unexpectedly slightly better than the 2-naphthylamido substituted analogue (IC50 = 650 μM).

Original languageEnglish
Pages (from-to)245-251
Number of pages7
JournalCarbohydrate Research
Volume402
DOIs
Publication statusPublished - Jan 30 2015

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Keywords

  • Carbohydrate
  • Click chemistry
  • Glycogen phosphorylase
  • Inhibitor
  • Triazole

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Organic Chemistry

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