Chemistry Department, The Hashemite University, PO Box 150459, Zarka 13115, Jordan.
Bioorg Med Chem. 2010 Jul 15;18(14):5367-78. doi: 10.1016/j.bmc.2010.05.040. Epub 2010 May 20.
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.
半乳糖 C3-三唑衍生物通过铜（I）催化的炔烃和半乳糖 C3-叠氮衍生物之间的环加成反应合成。对半乳糖凝集素-3、7、8N（N 端）和 9N（N 端）的评估表明，1,4-二取代三唑是半乳糖凝集素-3 的高亲和力抑制剂，对半乳糖凝集素-7、8N 和 9N 具有选择性。1,4-二取代和 1,4,5-三取代半乳糖 C3-三唑的构象分析表明，三唑 C5-取代基在空间上与半乳糖蛋白相互干扰，这解释了它们与相应的 1,4-二取代三唑相比亲和力较差。在硫代半乳糖苷上引入两个 1,4-二取代三唑部分，导致对半乳糖凝集素-3 的亲和力低至 29 nM。
