Amide-1,2,3-triazole bioisosterism: the glycogen phosphorylase case

Evangelia D. Chrysina, Éva Bokor, Kyra Melinda Alexacou, Maria Despoina Charavgi, George N. Oikonomakos, Spyros E. Zographos, Demetres D. Leonidas, Nikos G. Oikonomakos, László Somsák

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Abstract

Per-O-acetylated β-d-glucopyranosyl azide was transformed into an intermediate iminophosphorane by PMe3 which was then acylated to N-acyl-β-d-glucopyranosylamines. The same azide and substituted acetylenes gave 1-(β-d-glucopyranosyl)-4-substituted-1,2,3-triazoles in Cu(I)-catalyzed azide-alkyne cycloadditions. Deprotection of these products by the Zemplén method furnished β-d-Glcp-NHCO-R derivatives as well as 1-(β-d-Glcp)-4-R-1,2,3-triazoles which were evaluated as inhibitors of rabbit muscle glycogen phosphorylase b. Pairs of amides versus triazoles with the same R group displayed similar inhibition constants. X-ray crystallographic studies on the enzyme-inhibitor complexes revealed high similarities in the binding of pairs with R = 2-naphthyl and hydroxymethyl, while for the R = Ph and 1-naphthyl compounds a different orientation of the aromatic part and changes in the conformation of the 280s loop were observed. By this study new examples of amide-1,2,3-triazole bioisosteric relationship have been provided.

Original languageEnglish
Pages (from-to)733-740
Number of pages8
JournalTetrahedron Asymmetry
Volume20
Issue number6-8
DOIs
Publication statusPublished - May 7 2009

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ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Chrysina, E. D., Bokor, É., Alexacou, K. M., Charavgi, M. D., Oikonomakos, G. N., Zographos, S. E., Leonidas, D. D., Oikonomakos, N. G., & Somsák, L. (2009). Amide-1,2,3-triazole bioisosterism: the glycogen phosphorylase case. Tetrahedron Asymmetry, 20(6-8), 733-740. https://doi.org/10.1016/j.tetasy.2009.03.021