Synthesis of heterocyclic N-(β-d-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase

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Abstract

In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-β-d- glucopyranosylamine and propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl- β-d-glucopyranosylamine which was transformed by 1,3-dipolar cycloadditions with aromatic azides and nitrile-oxides to the corresponding O-peracetylated N-(β-d-glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides and N-(β-d-glucopyranosyl)-3-substituted-isoxazole-5-carboxamides, respectively. These compounds were O-deacetylated by Zemplén's protocol to be tested as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitors of the two series were N-(β-d-glucopyranosyl)-1-(3,5-dimethyl- phenyl)-1,2,3-triazole-4-carboxamide (K i = 34 μM) and N-(β-d-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide (K i = 164 μM).

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalCarbohydrate Research
Volume351
DOIs
Publication statusPublished - Apr 1 2012

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Isoxazoles
Glycogen Phosphorylase
Triazoles
Phosphorylase b
Nitriles
Azides
Cycloaddition
Cycloaddition Reaction
Oxides
Muscle
Rabbits
Muscles
glucopyranosylamine
propiolic acid

Keywords

  • 1,2,3-Triazole-4-carboxamide
  • Azide-alkyne cycloaddition
  • Glycogen phosphorylase
  • Isoxazole-5-carboxamide
  • N-(β-d-Glucopyranosyl) carboxamide
  • Nitrile-oxide-alkyne cycloaddition

ASJC Scopus subject areas

  • Biochemistry
  • Analytical Chemistry
  • Organic Chemistry

Cite this

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title = "Synthesis of heterocyclic N-(β-d-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase",
abstract = "In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-β-d- glucopyranosylamine and propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl- β-d-glucopyranosylamine which was transformed by 1,3-dipolar cycloadditions with aromatic azides and nitrile-oxides to the corresponding O-peracetylated N-(β-d-glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides and N-(β-d-glucopyranosyl)-3-substituted-isoxazole-5-carboxamides, respectively. These compounds were O-deacetylated by Zempl{\'e}n's protocol to be tested as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitors of the two series were N-(β-d-glucopyranosyl)-1-(3,5-dimethyl- phenyl)-1,2,3-triazole-4-carboxamide (K i = 34 μM) and N-(β-d-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide (K i = 164 μM).",
keywords = "1,2,3-Triazole-4-carboxamide, Azide-alkyne cycloaddition, Glycogen phosphorylase, Isoxazole-5-carboxamide, N-(β-d-Glucopyranosyl) carboxamide, Nitrile-oxide-alkyne cycloaddition",
author = "B{\'a}lint K{\'o}nya and Tibor Docsa and P{\'a}l Gergely and L{\'a}szl{\'o} Soms{\'a}k",
year = "2012",
month = "4",
day = "1",
doi = "10.1016/j.carres.2012.01.020",
language = "English",
volume = "351",
pages = "56--63",
journal = "Carbohydrate Research",
issn = "0008-6215",
publisher = "Elsevier BV",

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TY - JOUR

T1 - Synthesis of heterocyclic N-(β-d-glucopyranosyl)carboxamides for inhibition of glycogen phosphorylase

AU - Kónya, Bálint

AU - Docsa, Tibor

AU - Gergely, Pál

AU - Somsák, László

PY - 2012/4/1

Y1 - 2012/4/1

N2 - In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-β-d- glucopyranosylamine and propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl- β-d-glucopyranosylamine which was transformed by 1,3-dipolar cycloadditions with aromatic azides and nitrile-oxides to the corresponding O-peracetylated N-(β-d-glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides and N-(β-d-glucopyranosyl)-3-substituted-isoxazole-5-carboxamides, respectively. These compounds were O-deacetylated by Zemplén's protocol to be tested as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitors of the two series were N-(β-d-glucopyranosyl)-1-(3,5-dimethyl- phenyl)-1,2,3-triazole-4-carboxamide (K i = 34 μM) and N-(β-d-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide (K i = 164 μM).

AB - In a DCC-mediated coupling 2,3,4,6-tetra-O-acetyl-β-d- glucopyranosylamine and propiolic acid gave N-propynoyl-2,3,4,6-tetra-O-acetyl- β-d-glucopyranosylamine which was transformed by 1,3-dipolar cycloadditions with aromatic azides and nitrile-oxides to the corresponding O-peracetylated N-(β-d-glucopyranosyl)-1-substituted-1,2,3-triazole-4-carboxamides and N-(β-d-glucopyranosyl)-3-substituted-isoxazole-5-carboxamides, respectively. These compounds were O-deacetylated by Zemplén's protocol to be tested as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitors of the two series were N-(β-d-glucopyranosyl)-1-(3,5-dimethyl- phenyl)-1,2,3-triazole-4-carboxamide (K i = 34 μM) and N-(β-d-glucopyranosyl)-3-(indol-2-yl)-isoxazole-5-carboxamide (K i = 164 μM).

KW - 1,2,3-Triazole-4-carboxamide

KW - Azide-alkyne cycloaddition

KW - Glycogen phosphorylase

KW - Isoxazole-5-carboxamide

KW - N-(β-d-Glucopyranosyl) carboxamide

KW - Nitrile-oxide-alkyne cycloaddition

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U2 - 10.1016/j.carres.2012.01.020

DO - 10.1016/j.carres.2012.01.020

M3 - Article

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JO - Carbohydrate Research

JF - Carbohydrate Research

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