N-(4-fluorophenyl)-2-[(2-oxo-2H-chromen-7-yl)-oxy]acetamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-(4-fluorophenyl)-2-[(2-oxo-2H-chromen-7-yl)-oxy]acetamide
• 英文别名: N-(4-fluorophenyl)-2-((2-oxo-2H-chromen-7-yl)oxy)acetamide；N-(4-fluorophenyl)-2-(2-oxo-2H-chromen-7-yloxy)acetamide；N-(4-fluorophenyl)-2-(2-oxochromen-7-yl)oxyacetamide
• 化学式: C₁₇H₁₂FNO₄
• 分子量: 313.285
• InChiKey: VWEZUOFSJFHWBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-羟基香豆素 在 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 N-(4-fluorophenyl)-2-[(2-oxo-2H-chromen-7-yl)-oxy]acetamide
  参考文献：
  名称：

  取代吲哚及其类似物作为甲型流感病毒抑制剂的合成及生物学评价

  摘要：

  甲型流感病毒 (IAV) 是一种对人类具有高致病性的病毒，最容易发生突变，因此会导致迅速、严重的全球大流行，导致全球数百万人死亡。由于对现有抗流感药物的耐药性正在发展，迫切需要具有不同作用方式的创新抑制剂。在我们之前的工作中，先导化合物 6092B-E5 已被证明是一种有效的抗病毒试剂。在这项工作中，利用吲哚环的取代和生物等排原理，设计、合成了六个系列的新型抗 IAV 靶标产品并评估了它们的抗病毒作用。化合物 D1、D3、D9、G1、G3、G12 和 G23 被确定为有前景的抗 IAV 候选物，具有出色的抗 IAV 功效（IC50 值为 3.06-5.77 μm）和低细胞毒性（CC50 值高达和超过 100 μm） .

  DOI：

  10.1002/cbdv.201800577

文献信息

• Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX
  作者：Aikaterini Peperidou、Silvia Bua、Murat Bozdag、Dimitra Hadjipavlou-Litina、Claudiu Supuran

  DOI：10.3390/molecules23010153

  日期：——

  thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX). Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX inhibitors (KIs in the range of 30.2-30.5 nM) were detected in this study. Two compounds, 4b

  通过用碘代乙酸乙酯将烷基化的相应的6-或7-羟基香豆素开始，通过原始程序制备了一系列6-和7-取代的香豆素的羧酰胺衍生物，并将所得到的酯转化为相应的羧酸。然后与一系列芳族/脂族/杂环胺反应，得到所需的酰胺。研究了这些新衍生物作为两种酶的抑制剂，即人碳酸酐酶（hCAs）和大豆脂氧合酶（LOX）。化合物4a和4b是有效的LOX抑制剂，而本研究中检测到许多有效的hCA IX抑制剂（KIs在30.2-30.5 nM范围内）。两种化合物4b和5b表现出双重抑制现象。此外，这些香豆素没有显着抑制广泛的胞质亚型hCA I和II，而它们是弱的hCA IV抑制剂，因此成为hCA IX选择性抑制剂。由于hCA IX和LOX是经过验证的抗肿瘤靶标，因此这些结果对于研究涉及肿瘤发生的新型药物靶标很有希望。
• 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.