5-deoxy-1,2-O-isopropylidene-5-[4-(1-cyclohexene)-1H-1,2,3-triazol-1-yl]-α-D-xylofuranose | 1217589-51-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-deoxy-1,2-O-isopropylidene-5-[4-(1-cyclohexene)-1H-1,2,3-triazol-1-yl]-α-D-xylofuranose
• 英文别名: (3aR,5R,6S,6aR)-5-[[4-(cyclohexen-1-yl)triazol-1-yl]methyl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-ol
• CAS: 1217589-51-9
• 化学式: C₁₆H₂₃N₃O₄
• 分子量: 321.376
• InChiKey: WCWXNRKGFFLAKS-LXTVHRRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-azido-5-deoxy-1,2-O-isopropylidene-α-D-xylofuranose 、 1-乙炔基环己烷 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 以98%的产率得到5-deoxy-1,2-O-isopropylidene-5-[4-(1-cyclohexene)-1H-1,2,3-triazol-1-yl]-α-D-xylofuranose
  参考文献：
  名称：

  Synthesis, Biological Activity, and Molecular Modeling Studies of 1H-1,2,3-Triazole Derivatives of Carbohydrates as α-Glucosidases Inhibitors

  摘要：

  A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the a-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-triazoles conjugated with sugars, including D-xylose, D-galactose, D-allose, and D-ribose. Compounds were screened for alpha-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Methyl-2,3-O-isopropylidene-beta-D-riboluranosides, such as the 4-(1-cyclohexenyl)-1,2,3-triazole derivative, were among the most active compounds, showing up to 25-fold higher inhibitory potency than the complex oligosaccharide acarbose. Docking studies on a MAL12 homology model disclosed a binding mode consistent with a transition-state-mimicking mechanism. Finally, the actual pharmacological potential of this triazole series was demonstrated by the reduction of postprandial blood glucose levels in normal rats. These compounds could represent new chemical scaffolds for developing novel drugs against T2D.

  DOI：

  10.1021/jm901265h

文献信息

• Synthesis, Biological Activity, and Molecular Modeling Studies of 1<i>H</i>-1,2,3-Triazole Derivatives of Carbohydrates as α-Glucosidases Inhibitors
  作者：Sabrina B. Ferreira、Ana C. R. Sodero、Mariana F. C. Cardoso、Emerson S. Lima、Carlos R. Kaiser、Floriano P. Silva、Vitor F. Ferreira

  DOI：10.1021/jm901265h

  日期：2010.3.25

  A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the a-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-triazoles conjugated with sugars, including D-xylose, D-galactose, D-allose, and D-ribose. Compounds were screened for alpha-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Methyl-2,3-O-isopropylidene-beta-D-riboluranosides, such as the 4-(1-cyclohexenyl)-1,2,3-triazole derivative, were among the most active compounds, showing up to 25-fold higher inhibitory potency than the complex oligosaccharide acarbose. Docking studies on a MAL12 homology model disclosed a binding mode consistent with a transition-state-mimicking mechanism. Finally, the actual pharmacological potential of this triazole series was demonstrated by the reduction of postprandial blood glucose levels in normal rats. These compounds could represent new chemical scaffolds for developing novel drugs against T2D.