7-(2-([1,1'-biphenyl]-4-yl)-2-oxoethoxy)-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-(2-([1,1'-biphenyl]-4-yl)-2-oxoethoxy)-2H-chromen-2-one
• 英文别名: 7-[2-oxo-2-(4-phenylphenyl)ethoxy]chromen-2-one
• 化学式: C₂₃H₁₆O₄
• 分子量: 356.378
• InChiKey: QIMQMTYCMVNFNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(2-([1,1'-biphenyl]-4-yl)-2-oxoethoxy)-2H-chromen-2-one 在 硫酸 、 sodium azide 作用下， 反应 1.17h， 以65%的产率得到N-(biphenyl-4-yl)-2-(2-oxo-2H-chromen-7-yloxy)acetamide
  参考文献：
  名称：

  Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model

  摘要：

  We have designed and synthesized certain novel oxime- and amide-bearing coumarin derivatives as nuclear factor erythroid 2 p45-related factor 2 (Nrf2) activators. The potency of these compounds was measured by antioxidant responsive element (ARE)-driven luciferase activity, level of Nrf2-related cytoprotective genes and proteins, and antioxidant activity. Among them, (Z)-3-(2-(hydroxyimino)-2-phenylethoxy)-2H-chromen-2-one (17a) was the most active, and more potent than the positive t-BHQ in the induction of ARE-driven luciferase activity. Exposure of HSC-3 cells to various concentrations of 17a strongly increased Nrf2 nuclear translocation and the expression level of Nrf2-mediated cytoprotective proteins in a concentration-dependent manner. HSC-3 cells pretreated with 17a significantly reduced t-BOOH-induced oxidative stress. In the animal experiment, Nrf2-mediated cytoprotective proteins, such as aldo-keto reductase 1 subunit C-1 (AKR1C1), glutathione reductase (GR), and heme oxygenase (HO-1), were obviously elevated in the liver of 17a-treated mice than that of control. These results suggested that novel oxime-bearing coumarin 17a is able to activate Nrf2/ARE pathway in vivo and are therefore seen as a promising candidate for further investigation. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.029
• 作为产物：
  描述：

  7-羟基香豆素 、 2-溴-4-苯基乙酰苯 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以89%的产率得到7-(2-([1,1'-biphenyl]-4-yl)-2-oxoethoxy)-2H-chromen-2-one
  参考文献：
  名称：

  Synthesis and Evaluation of Coumarin .ALPHA.-Methylene-.GAMMA.-butyrolactones: A New Class of Platelet Aggregation Inhibitors.

  摘要：

  在寻找新的血小板聚集抑制剂的过程中，合成了某些含香豆素的α-亚甲基-γ-丁内酯，并评估其对洗涤兔血小板中由凝血酶（Thr）、花生四烯酸（AA）、胶原（Col）和血小板激活因子（PAF）诱导的聚集的抑制活性。这些化合物是从商业可得的7-羟基香豆素或其衍生物高效合成的。在这些化合物中，7-[（2, 3, 4, 5-四氢-4-亚甲基-5-氧代-2-苯基-2-呋喃基）甲氧基]-2H-1-苯并吡喃-2-酮（3d）显示出对AA和PAF诱导的聚集最强的抑制作用，其IC50值分别为3.65μM和16.36μM。

  DOI：

  10.1248/cpb.44.1591

文献信息

• Synthesis and Evaluation of Coumarin .ALPHA.-Methylene-.GAMMA.-butyrolactones: A New Class of Platelet Aggregation Inhibitors.
  作者：Yeh-Long CHEN、Tai-Chi WANG、Shiu-Chuan LIANG、Che-Ming TENG、Cherng-Chyi TZENG

  DOI：10.1248/cpb.44.1591

  日期：——

  In a search for new inhibitors of platelet aggregation, certain coumarin-bearing α-methylene-γ-butyrolactones were synthesized and evaluated for inhibitory activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were efficiently synthesized from commercially available 7-hydroxycoumarin or its derivative. Among them, 7-[(2, 3, 4, 5-tetrahydro-4-methylene-5-oxo-2-phenyl-2-furanyl)methoxy]-2H-1-benzopyran-2-one (3d) showed the most potent inhibition of AA- and PAF- induced aggregation, with IC50 values of 3.65 and 16.36μM respectively.

  在寻找新的血小板聚集抑制剂的过程中，合成了某些含香豆素的α-亚甲基-γ-丁内酯，并评估其对洗涤兔血小板中由凝血酶（Thr）、花生四烯酸（AA）、胶原（Col）和血小板激活因子（PAF）诱导的聚集的抑制活性。这些化合物是从商业可得的7-羟基香豆素或其衍生物高效合成的。在这些化合物中，7-[（2, 3, 4, 5-四氢-4-亚甲基-5-氧代-2-苯基-2-呋喃基）甲氧基]-2H-1-苯并吡喃-2-酮（3d）显示出对AA和PAF诱导的聚集最强的抑制作用，其IC50值分别为3.65μM和16.36μM。
• Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model
  作者：Ken-Ming Chang、Huang-Hui Chen、Tai-Chi Wang、I-Li Chen、Yu-Tsen Chen、Shyh-Chyun Yang、Yeh-Long Chen、Hsin-Huei Chang、Chih-Hsiang Huang、Jang-Yang Chang、Chuan Shih、Ching-Chuan Kuo、Cherng-Chyi Tzeng

  DOI：10.1016/j.ejmech.2015.10.029

  日期：2015.12

  We have designed and synthesized certain novel oxime- and amide-bearing coumarin derivatives as nuclear factor erythroid 2 p45-related factor 2 (Nrf2) activators. The potency of these compounds was measured by antioxidant responsive element (ARE)-driven luciferase activity, level of Nrf2-related cytoprotective genes and proteins, and antioxidant activity. Among them, (Z)-3-(2-(hydroxyimino)-2-phenylethoxy)-2H-chromen-2-one (17a) was the most active, and more potent than the positive t-BHQ in the induction of ARE-driven luciferase activity. Exposure of HSC-3 cells to various concentrations of 17a strongly increased Nrf2 nuclear translocation and the expression level of Nrf2-mediated cytoprotective proteins in a concentration-dependent manner. HSC-3 cells pretreated with 17a significantly reduced t-BOOH-induced oxidative stress. In the animal experiment, Nrf2-mediated cytoprotective proteins, such as aldo-keto reductase 1 subunit C-1 (AKR1C1), glutathione reductase (GR), and heme oxygenase (HO-1), were obviously elevated in the liver of 17a-treated mice than that of control. These results suggested that novel oxime-bearing coumarin 17a is able to activate Nrf2/ARE pathway in vivo and are therefore seen as a promising candidate for further investigation. (C) 2015 Elsevier Masson SAS. All rights reserved.