2-((2-oxo-2H-chromen-7-yl)oxy)-N-phenylacetamide

• 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: 2-((2-oxo-2H-chromen-7-yl)oxy)-N-phenylacetamide
• 英文别名: 2-[(2-oxo-2H-chromen-7-yl)oxy]-N-phenylacetamide；2-(2-oxo-2H-chromen-7-yloxy)-N-phenylacetamide；2-(2-oxochromen-7-yl)oxy-N-phenylacetamide
• 化学式: C₁₇H₁₃NO₄
• 分子量: 295.295
• InChiKey: UURRCYDABCSNQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 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：
  4

反应信息

• 作为产物：
  描述：

  7-(2-oxo-2-phenylethoxy)-2H-1-benzopyran-2-one 在 硫酸 、 sodium azide 作用下， 反应 1.17h， 以88%的产率得到2-((2-oxo-2H-chromen-7-yl)oxy)-N-phenylacetamide
  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

文献信息

• Coumarin and 3,4-dihydroquinolinone derivatives: Synthesis, antidepressant activity, and molecular docking studies
  作者：Shi-Ben Wang、Hui Liu、Guang-Yong Li、Jun Li、Xiao-Jing Li、Kang Lei、Li-Chao Wei、Zhe-Shan Quan、Xue-Kun Wang、Ren-Min Liu

  DOI：10.1016/j.pharep.2019.07.011

  日期：2019.12

  (Compounds 8, 9, 11, 14, 15, 18-20, 23, 24 and 28 are new compounds) and studied their antidepressant activities. METHODS Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The most active compound was used to evaluate the exploratory activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate

  背景香豆素和3,4-二氢喹啉酮核是两个重要的杂环，并广泛用于生物活性分子的开发。在这里，我们设计并合成了一系列3,4-二氢喹啉酮和香豆素衍生物（化合物8、9、11、14、15、18-20、23、24和28为新化合物）并研究了它们的抗抑郁活性。方法采用强迫游泳试验(FST)和悬尾试验(TST)评价目标化合物的抗抑郁活性。最活跃的化合物用于通过旷场测试评估动物的探索活动。通过使用 ELISA 估算 5-HT 浓度，以评估该化合物是否对小鼠大脑有影响。还进行了 5-HT1A 结合测定。通过分子对接研究验证了化合物的生物活性。Discovery Studio 和 ChemBioDraw Ultra 预测了目标化合物的理化和药代动力学特性。结果 在所有测试的化合物中，化合物7表现出最好的抗抑郁活性，其在FST中使不动时间减少了65.52 s。然而，在旷场试验中，化合物7并不影响自发活动。体内5-HT
• 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.