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Journal articles
Synthesis of 4-amidomethyl-1-glucosyl-1,2,3-triazoles and evaluation as glycogen phosphorylase inhibitors
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).
https://hal-udl.archives-ouvertes.fr/hal-02123965
Contributor : Umr5246 Icbms <>
Submitted on : Friday, May 10, 2019 - 12:53:38 PM
Last modification on : Wednesday, July 8, 2020 - 12:43:59 PM
Contributor : Umr5246 Icbms <>
Submitted on : Friday, May 10, 2019 - 12:53:38 PM
Last modification on : Wednesday, July 8, 2020 - 12:43:59 PM
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