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ID: ALA1152413

Journal: Bioorg Med Chem

Title: Glucose-based spiro-heterocycles as potent inhibitors of glycogen phosphorylase.

Authors: Nagy V, Benltifa M, Vidal S, Berzsényi E, Teilhet C, Czifrák K, Batta G, Docsa T, Gergely P, Somsák L, Praly JP.

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 (K(i)=160 nM), among glucose-based inhibitors known to date.

CiteXplore: 19574053

DOI: 10.1016/j.bmc.2009.05.080