Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy- β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase

Z. Györgydeák, Zsuzsa Hadady, Nóra Felfóldi, Attila Krakomperger, V. Nagy, M. Tóth, Attila Brunyánszki, T. Docsa, P. Gergely, L. Somsák

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl- and 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(β-D-glycopyranosyl) amides via a PMe 3 mediated Staudinger protocol (generation of N-(β-D- glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zemplén deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(β-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (K i = 3.5 μM).

Original languageEnglish
Pages (from-to)4861-4870
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number18
DOIs
Publication statusPublished - Sep 15 2004

Fingerprint

Glycogen Phosphorylase
Amides
Phosphorylase b
Acylation
Azides
Anhydrides
Carboxylic Acids
Muscle
Chlorides
Rabbits
Muscles
Acids

Keywords

  • Glycogen phosphorylase
  • Inhibitors
  • N-Glycosylamides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy- β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase. / Györgydeák, Z.; Hadady, Zsuzsa; Felfóldi, Nóra; Krakomperger, Attila; Nagy, V.; Tóth, M.; Brunyánszki, Attila; Docsa, T.; Gergely, P.; Somsák, L.

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 18, 15.09.2004, p. 4861-4870.

Research output: Contribution to journalArticle

@article{99b7707c951c42d591d1312cc982b14d,
title = "Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy- β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase",
abstract = "2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl- and 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(β-D-glycopyranosyl) amides via a PMe 3 mediated Staudinger protocol (generation of N-(β-D- glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zempl{\'e}n deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(β-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (K i = 3.5 μM).",
keywords = "Glycogen phosphorylase, Inhibitors, N-Glycosylamides",
author = "Z. Gy{\"o}rgyde{\'a}k and Zsuzsa Hadady and N{\'o}ra Felf{\'o}ldi and Attila Krakomperger and V. Nagy and M. T{\'o}th and Attila Bruny{\'a}nszki and T. Docsa and P. Gergely and L. Soms{\'a}k",
year = "2004",
month = "9",
day = "15",
doi = "10.1016/j.bmc.2004.07.013",
language = "English",
volume = "12",
pages = "4861--4870",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "18",

}

TY - JOUR

T1 - Synthesis of N-(β-D-glucopyranosyl)- and N-(2-acetamido-2-deoxy- β-D-glucopyranosyl) amides as inhibitors of glycogen phosphorylase

AU - Györgydeák, Z.

AU - Hadady, Zsuzsa

AU - Felfóldi, Nóra

AU - Krakomperger, Attila

AU - Nagy, V.

AU - Tóth, M.

AU - Brunyánszki, Attila

AU - Docsa, T.

AU - Gergely, P.

AU - Somsák, L.

PY - 2004/9/15

Y1 - 2004/9/15

N2 - 2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl- and 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(β-D-glycopyranosyl) amides via a PMe 3 mediated Staudinger protocol (generation of N-(β-D- glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zemplén deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(β-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (K i = 3.5 μM).

AB - 2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl- and 2-acetamido-3,4,6-tri- O-acetyl-2-deoxy-β-D-glucopyranosyl azides were transformed into the corresponding per-O-acetylated N-(β-D-glycopyranosyl) amides via a PMe 3 mediated Staudinger protocol (generation of N-(β-D- glycopyranosyl)imino-trimethylphosphoranes followed by acylation with carboxylic acids, acid chlorides or anhydrides). The deprotected compounds obtained by Zemplén deacetylation were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. The best inhibitor of this series has been N-(β-D-glucopyranosyl) 3-(2-naphthyl)-propenoic amide (K i = 3.5 μM).

KW - Glycogen phosphorylase

KW - Inhibitors

KW - N-Glycosylamides

UR - http://www.scopus.com/inward/record.url?scp=4444342876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444342876&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2004.07.013

DO - 10.1016/j.bmc.2004.07.013

M3 - Article

C2 - 15336265

AN - SCOPUS:4444342876

VL - 12

SP - 4861

EP - 4870

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 18

ER -