2-(2-fluorophenyl)-5-hydroxy-6H-xantheno [4, 3-d] oxazol-6-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-(2-fluorophenyl)-5-hydroxy-6H-xantheno [4, 3-d] oxazol-6-one
• 英文别名: 2-(2-Fluorophenyl)-5-hydroxychromeno[2,3-e][1,3]benzoxazol-6-one；2-(2-fluorophenyl)-5-hydroxychromeno[2,3-e][1,3]benzoxazol-6-one
• 化学式: C₂₀H₁₀FNO₄
• 分子量: 347.302
• InChiKey: JXCVSVNRDZTSCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,3-二羟基氧杂蒽-9-酮 在 Eaton’s reagent 、 palladium on activated charcoal 、 氢气 、 硝酸 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 40.0~110.0 ℃ 、100.0 kPa 条件下， 反应 17.0h， 生成 2-(2-fluorophenyl)-5-hydroxy-6H-xantheno [4, 3-d] oxazol-6-one
  参考文献：
  名称：

  Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis, activities, inhibitory modes and synergetic effect

  摘要：

  Xanthone derivatives have shown good alpha-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as alpha-glucosidase inhibitors. Inhibition assays indicated that compounds 4-21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5-21 (IC50 = 6.3 +/- 0.4-38.5 +/- 4.6 mu M) were more active than 1-deoxynojirimycin (IC50 = 60.2 +/- 6.2 mu M), a well-known a-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver-Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4: 6 led to an IC50 value of 1.9 +/- 0.7 mu M, better than the IC50 value of 7.1 +/- 0.9 mu M for compound 16 and 8.6 +/- 0.9 mu M for compound 20. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.05.008

文献信息

• Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis, activities, inhibitory modes and synergetic effect
  作者：Sen-Miao Ding、Tian Lan、Gao-Jie Ye、Jia-Jun Huang、You Hu、Yi-Ran Zhu、Bo Wang

  DOI：10.1016/j.bmc.2018.05.008

  日期：2018.7

  Xanthone derivatives have shown good alpha-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as alpha-glucosidase inhibitors. Inhibition assays indicated that compounds 4-21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5-21 (IC50 = 6.3 +/- 0.4-38.5 +/- 4.6 mu M) were more active than 1-deoxynojirimycin (IC50 = 60.2 +/- 6.2 mu M), a well-known a-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver-Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4: 6 led to an IC50 value of 1.9 +/- 0.7 mu M, better than the IC50 value of 7.1 +/- 0.9 mu M for compound 16 and 8.6 +/- 0.9 mu M for compound 20. (C) 2018 Elsevier Ltd. All rights reserved.