1-(2,5-dimethoxyphenyl)-2-(naphthalen-1-yloxy)ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2,5-dimethoxyphenyl)-2-(naphthalen-1-yloxy)ethanone
• 英文别名: 1-(2,5-Dimethoxyphenyl)-2-naphthalen-1-yloxyethanone
• 化学式: C₂₀H₁₈O₄
• 分子量: 322.361
• InChiKey: KPNKVHBZBNGADY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2,5-dimethoxyphenyl)-2-(naphthalen-1-yloxy)ethanone 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以59%的产率得到(Z)-1-(2,5-dimethoxyphenyl)-2-(naphthalen-1-yloxy)ethanone oxime
  参考文献：
  名称：

  Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators

  摘要：

  Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application. Compound which can activate Nrf2 signaling pathway result unregulated the cellular antioxidant-responses has been demonstrated as an effective chemopreventive approach for cancer treatment. In the present study, certain oxime-bearing naphthalene derivatives were synthesized and evaluated for their Nrf2 activation and anti-proliferative activities. Results indicated (E)-1-(naphthalen-2-yloxy) propan-2-one oxime (11) which increased 2.04-fold Nrf2/ARE-driven luciferase activity was more active than its 1-substituted isomer 10 (1.17-fold) and t-BHQ (1.77-fold), the known Nrf2 activator. The activities were further increased by the replacement of the peripheral methyl group with the phenyl ring in which (Z)-2-(naphthalen-2-yloxy)-1-phenylethanone oxime (13a) exhibited 3.49-fold potency of the positive control. It is worth to mention that compounds 11, 13a, and 13b which showed significant Nrf2 activation are non-cytotoxic to the tested cells with IC50 > 50 mu M. This observation strongly suggested that these compounds can be used for chemoprevention. Mechanism studies indicated that these compounds were capable of inducing the phosphorylation of Nrf2 protein at serine 40 which led to the activation of the Nrf2 transcriptional activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.046
• 作为产物：
  描述：

  萘酚 、 2-溴-2',5'-二甲氧基苯乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 以73%的产率得到1-(2,5-dimethoxyphenyl)-2-(naphthalen-1-yloxy)ethanone
  参考文献：
  名称：

  Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators

  摘要：

  Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application. Compound which can activate Nrf2 signaling pathway result unregulated the cellular antioxidant-responses has been demonstrated as an effective chemopreventive approach for cancer treatment. In the present study, certain oxime-bearing naphthalene derivatives were synthesized and evaluated for their Nrf2 activation and anti-proliferative activities. Results indicated (E)-1-(naphthalen-2-yloxy) propan-2-one oxime (11) which increased 2.04-fold Nrf2/ARE-driven luciferase activity was more active than its 1-substituted isomer 10 (1.17-fold) and t-BHQ (1.77-fold), the known Nrf2 activator. The activities were further increased by the replacement of the peripheral methyl group with the phenyl ring in which (Z)-2-(naphthalen-2-yloxy)-1-phenylethanone oxime (13a) exhibited 3.49-fold potency of the positive control. It is worth to mention that compounds 11, 13a, and 13b which showed significant Nrf2 activation are non-cytotoxic to the tested cells with IC50 > 50 mu M. This observation strongly suggested that these compounds can be used for chemoprevention. Mechanism studies indicated that these compounds were capable of inducing the phosphorylation of Nrf2 protein at serine 40 which led to the activation of the Nrf2 transcriptional activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.046

文献信息

• Discovery of oxime-bearing naphthalene derivatives as a novel structural type of Nrf2 activators
  作者：Ken-Ming Chang、Fong-Pin Liang、I-Li Chen、Shyh-Chyun Yang、Shin-Hun Juang、Tai-Chi Wang、Yeh-Long Chen、Cherng-Chyi Tzeng

  DOI：10.1016/j.bmc.2015.03.046

  日期：2015.7

  Recent studies have demonstrated that oxidative stress insult is one of major causes of tumor formation. Therefore, identify the effective anti-oxidative agents as a preventive approach to stop cancer progression has widely explored. Although, many potent anti-oxidative ingredients in the natural products have been identified but the amount from the nature source hindrances the clinical application. Compound which can activate Nrf2 signaling pathway result unregulated the cellular antioxidant-responses has been demonstrated as an effective chemopreventive approach for cancer treatment. In the present study, certain oxime-bearing naphthalene derivatives were synthesized and evaluated for their Nrf2 activation and anti-proliferative activities. Results indicated (E)-1-(naphthalen-2-yloxy) propan-2-one oxime (11) which increased 2.04-fold Nrf2/ARE-driven luciferase activity was more active than its 1-substituted isomer 10 (1.17-fold) and t-BHQ (1.77-fold), the known Nrf2 activator. The activities were further increased by the replacement of the peripheral methyl group with the phenyl ring in which (Z)-2-(naphthalen-2-yloxy)-1-phenylethanone oxime (13a) exhibited 3.49-fold potency of the positive control. It is worth to mention that compounds 11, 13a, and 13b which showed significant Nrf2 activation are non-cytotoxic to the tested cells with IC50 > 50 mu M. This observation strongly suggested that these compounds can be used for chemoprevention. Mechanism studies indicated that these compounds were capable of inducing the phosphorylation of Nrf2 protein at serine 40 which led to the activation of the Nrf2 transcriptional activity. (C) 2015 Elsevier Ltd. All rights reserved.