Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase

The aim of the present study was to broaden the structure-activity relationships of C- and N-β-d-glucopyranosyl azole type inhibitors of glycogen phosphorylase. 1-Aryl-4-β-d-gluco-pyranosyl-1,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-per...

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Main Authors:	Sándor Kun, Éva Bokor, Ádám Sipos, Tibor Docsa, László Somsák
Format:	Article
Language:	English
Published:	MDPI AG 2018-03-01
Series:	Molecules
Subjects:	C-glucosyl heterocycle N-glucosyl heterocycle 1,2,3-triazole imidazole tetrazole glycogen phosphorylase inhibitor structure-activity relationship
Online Access:	http://www.mdpi.com/1420-3049/23/3/666

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spelling	doaj-8e16ad3347f840dba31651fb477c2b472020-11-24T21:23:51ZengMDPI AGMolecules1420-30492018-03-0123366610.3390/molecules23030666molecules23030666Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen PhosphorylaseSándor Kun0Éva Bokor1Ádám Sipos2Tibor Docsa3László Somsák4Department of Organic Chemistry, University of Debrecen, P.O. Box 400, H-4002 Debrecen, HungaryDepartment of Organic Chemistry, University of Debrecen, P.O. Box 400, H-4002 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, HungaryDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, HungaryDepartment of Organic Chemistry, University of Debrecen, P.O. Box 400, H-4002 Debrecen, HungaryThe aim of the present study was to broaden the structure-activity relationships of C- and N-β-d-glucopyranosyl azole type inhibitors of glycogen phosphorylase. 1-Aryl-4-β-d-gluco-pyranosyl-1,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-d-glucopyranosyl ethynes and aryl azides. 1-β-d-Gluco-pyranosyl-4-phenyl imidazole was obtained in a glycosylation of 4(5)-phenylimidazole with O-peracetylated α-d-glucopyranosyl bromide. C-β-d-Glucopyranosyl-N-substituted-tetrazoles were synthesized by alkylation/arylation of O-perbenzoylated 5-β-d-glucopyranosyl-tetrazole or from a 2,6-anhydroheptose tosylhydrazone and arenediazonium salts. 5-Substituted tetrazoles were glycosylated by O-peracetylated α-d-glucopyranosyl bromide to give N-β-d-glucopyranosyl-C-substituted-tetrazoles. Standard deprotections gave test compounds which were assayed against rabbit muscle glycogen phosphorylase b. Most of the compounds proved inactive, the best inhibitor was 2-β-d-glucopyranosyl-5-phenyltetrazole (IC50 600 μM). These studies extended the structure-activity relationships of β-d-glucopyranosyl azole type inhibitors and revealed the extreme sensitivity of such type of inhibitors towards the structure of the azole moiety.http://www.mdpi.com/1420-3049/23/3/666C-glucosyl heterocycleN-glucosyl heterocycle1,2,3-triazoleimidazoletetrazoleglycogen phosphorylaseinhibitorstructure-activity relationship
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Sándor Kun Éva Bokor Ádám Sipos Tibor Docsa László Somsák
spellingShingle	Sándor Kun Éva Bokor Ádám Sipos Tibor Docsa László Somsák Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase Molecules C-glucosyl heterocycle N-glucosyl heterocycle 1,2,3-triazole imidazole tetrazole glycogen phosphorylase inhibitor structure-activity relationship
author_facet	Sándor Kun Éva Bokor Ádám Sipos Tibor Docsa László Somsák
author_sort	Sándor Kun
title	Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
title_short	Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
title_full	Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
title_fullStr	Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
title_full_unstemmed	Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase
title_sort	synthesis of new c- and n-β-d-glucopyranosyl derivatives of imidazole, 1,2,3-triazole and tetrazole, and their evaluation as inhibitors of glycogen phosphorylase
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2018-03-01
description	The aim of the present study was to broaden the structure-activity relationships of C- and N-β-d-glucopyranosyl azole type inhibitors of glycogen phosphorylase. 1-Aryl-4-β-d-gluco-pyranosyl-1,2,3-triazoles were prepared by copper catalyzed azide-alkyne cycloadditions between O-perbenzylated or O-peracetylated β-d-glucopyranosyl ethynes and aryl azides. 1-β-d-Gluco-pyranosyl-4-phenyl imidazole was obtained in a glycosylation of 4(5)-phenylimidazole with O-peracetylated α-d-glucopyranosyl bromide. C-β-d-Glucopyranosyl-N-substituted-tetrazoles were synthesized by alkylation/arylation of O-perbenzoylated 5-β-d-glucopyranosyl-tetrazole or from a 2,6-anhydroheptose tosylhydrazone and arenediazonium salts. 5-Substituted tetrazoles were glycosylated by O-peracetylated α-d-glucopyranosyl bromide to give N-β-d-glucopyranosyl-C-substituted-tetrazoles. Standard deprotections gave test compounds which were assayed against rabbit muscle glycogen phosphorylase b. Most of the compounds proved inactive, the best inhibitor was 2-β-d-glucopyranosyl-5-phenyltetrazole (IC50 600 μM). These studies extended the structure-activity relationships of β-d-glucopyranosyl azole type inhibitors and revealed the extreme sensitivity of such type of inhibitors towards the structure of the azole moiety.
topic	C-glucosyl heterocycle N-glucosyl heterocycle 1,2,3-triazole imidazole tetrazole glycogen phosphorylase inhibitor structure-activity relationship
url	http://www.mdpi.com/1420-3049/23/3/666
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Synthesis of New C- and N-β-d-Glucopyranosyl Derivatives of Imidazole, 1,2,3-Triazole and Tetrazole, and Their Evaluation as Inhibitors of Glycogen Phosphorylase

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