1,3-dihydroxy-4-nitro-9H-xanthen-9-one | 1068126-17-9

• 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: 1,3-dihydroxy-4-nitro-9H-xanthen-9-one
• 英文别名: 1,3-Dihydroxy-4-nitroxanthen-9-one
• CAS: 1068126-17-9
• 化学式: C₁₃H₇NO₆
• 分子量: 273.202
• InChiKey: JQVNKQLMDXUURL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,3-dihydroxy-4-nitro-9H-xanthen-9-one 在 palladium on activated charcoal 、 氢气 作用下， 以 丙酮 为溶剂， 40.0 ℃ 、100.0 kPa 条件下， 反应 12.0h， 以90.5%的产率得到1,3-dihydroxy-4-amino-9H-xanthen-9-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
• 作为产物：
  描述：

  1,3-二羟基氧杂蒽-9-酮 在 硝酸 、 溶剂黄146 作用下， 反应 1.0h， 以61%的产率得到1,3-dihydroxy-4-nitro-9H-xanthen-9-one
  参考文献：
  名称：

  Synthesis, inhibitory activities, and QSAR study of xanthone derivatives as α-glucosidase inhibitors

  摘要：

  Xanthones and their derivatives have been reported to exhibit strong inhibitory activities toward alpha-glucosidase. To provide deep insight into the correlation between inhibitory activities and structures of xanthones, multiple linear regression (MLR) method was employed to establish QSAR models for 43 xanthone derivatives that have diverse structures. Among the 38 typical descriptors investigated, Hs (number of H-bond forming substituents), N-pi (number of aromatic rings), and S (softness value) can be utilized to model the inhibitory activity. Thus, inhibitory activities of xanthone derivatives can be regulated by H-bond forming substituents, pi-stacking-forming aromatic rings and softness values on the xanthone skeleton. The accuracy and predictive power of the proposed QSAR model were verified by LOO validation, Y-randomization, and test group validation with newly synthesized xanthone derivatives. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.06.043

文献信息

• Synthesis, inhibitory activities, and QSAR study of xanthone derivatives as α-glucosidase inhibitors
  作者：Yan Liu、Zhuofeng Ke、Jianfang Cui、Wen-Hua Chen、Lin Ma、Bo Wang

  DOI：10.1016/j.bmc.2008.06.043

  日期：2008.8

  Xanthones and their derivatives have been reported to exhibit strong inhibitory activities toward alpha-glucosidase. To provide deep insight into the correlation between inhibitory activities and structures of xanthones, multiple linear regression (MLR) method was employed to establish QSAR models for 43 xanthone derivatives that have diverse structures. Among the 38 typical descriptors investigated, Hs (number of H-bond forming substituents), N-pi (number of aromatic rings), and S (softness value) can be utilized to model the inhibitory activity. Thus, inhibitory activities of xanthone derivatives can be regulated by H-bond forming substituents, pi-stacking-forming aromatic rings and softness values on the xanthone skeleton. The accuracy and predictive power of the proposed QSAR model were verified by LOO validation, Y-randomization, and test group validation with newly synthesized xanthone derivatives. (C) 2008 Elsevier Ltd. All rights reserved.
• 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.