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ID: ALA1250422

Journal: Bioorg Med Chem

Title: 1H-1,2,3-triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors.

Authors: Salameh BA, Cumpstey I, Sundin A, Leffler H, Nilsson UJ.

Abstract: Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di- and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3.

CiteXplore: 20538469

DOI: 10.1016/j.bmc.2010.05.040