Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase

V. Nagy, Mahmoud Benltifa, Sébastien Vidal, Eszter Berzsényi, Cathie Teilhet, K. Czifrák, G. Batta, T. Docsa, P. Gergely, L. Somsák, Jean Pierre Praly

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Glucopyranosylidene-spiro-1,4,2-oxathiazoles were prepared in high yields by NBS-mediated spiro-cyclization of the corresponding glucosyl-hydroximothioates. In an effort to synthesize analogous glucopyranosylidene-spiro-1,2,4-oxadiazolines, with a nitrogen atom instead of the sulphur, attempted cyclizations resulted in aromatization of the heterocycle with opening of the pyranosyl ring. Enzymatic measurements showed that some of the glucose-based inhibitors were active in the micromolar range. The 2-naphthyl-substituted 1,4,2-oxathiazole displayed the best inhibition against RMGPb (Ki = 160 nM), among glucose-based inhibitors known to date.

Original languageEnglish
Pages (from-to)5696-5707
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number15
DOIs
Publication statusPublished - Aug 1 2009

Fingerprint

Glycogen Phosphorylase
Cyclization
Aromatization
Glucose
Sulfur
Nitrogen
Atoms

Keywords

  • Carbohydrates
  • Glucosyl-hydroximothioates
  • Glucosylidene-spirooxathiazoles
  • Glycogen phosphorylase
  • Glycomimics
  • Inhibitors
  • Spiro-compounds
  • Spiro-cyclization

ASJC Scopus subject areas

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

Cite this

Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase. / Nagy, V.; Benltifa, Mahmoud; Vidal, Sébastien; Berzsényi, Eszter; Teilhet, Cathie; Czifrák, K.; Batta, G.; Docsa, T.; Gergely, P.; Somsák, L.; Praly, Jean Pierre.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 15, 01.08.2009, p. 5696-5707.

Research output: Contribution to journalArticle

Nagy, V. ; Benltifa, Mahmoud ; Vidal, Sébastien ; Berzsényi, Eszter ; Teilhet, Cathie ; Czifrák, K. ; Batta, G. ; Docsa, T. ; Gergely, P. ; Somsák, L. ; Praly, Jean Pierre. / Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 15. pp. 5696-5707.
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