(7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxyethyl)docosa-7,10,13,16,19-pentaenamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxyethyl)docosa-7,10,13,16,19-pentaenamide
• 英文别名: cis-docosa-7,10,13,16,19-pentaenoic acid (2-hydroxy ethyl)amide；(7Z,10Z,13Z,16Z,19Z)-N-(2-Hydroxyethyl)docosa-7,10,13,16,19-pentaenamide
• 化学式: C₂₄H₃₉NO₂
• 分子量: 373.579
• InChiKey: XZURZCGSKALDLA-JLNKQSITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  methyl (2E,7Z,10Z,13Z,16Z,19Z)-docosa-2,7,10,13,16,19-hexaenoate 在 lithium hydroxide monohydrate 、 magnesium 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 27.5h， 生成 (7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxyethyl)docosa-7,10,13,16,19-pentaenamide
  参考文献：
  名称：

  合成脂肪酸酰胺的便捷方案

  摘要：

  已经从哺乳动物和植物来源报道了几类生物存在的脂肪酸酰胺。许多与哺乳动物来源的脂肪酸结合的酰胺表现出对个体受体的特异性激活。它们作为药理学工具或作为开发新疗法的先导化合物的潜力引起了人们极大的兴趣。因此，需要在不影响敏感功能的几何形状或位置的情况下，通过实用、高产和可扩展的协议来获取此类酰胺。满足所有这些要求的方案包括用羰基二咪唑 (CDI) 活化相应的酸，然后与所需的胺或其盐酸盐反应。已经以通常高产率制备了五十多种化合物。

  DOI：

  10.1055/s-0037-1611939

文献信息

• One-pot synthesis of polyunsaturated fatty acid amides with anti-proliferative properties
  作者：Hugo Tremblay、Catherine St-Georges、Marc-André Legault、Caroline Morin、Samuel Fortin、Eric Marsault

  DOI：10.1016/j.bmcl.2014.10.084

  日期：2014.12

  A one-pot environmentally friendly transamidation of ω-3 fatty acid ethyl esters to amides and mono- or diacylglycerols was investigated via the use of a polymer-supported lipase. The method was used to synthesize a library of fatty acid monoglyceryl esters and amides. These new derivatives were found to have potent growth inhibition effects against A549 lung cancer cells.

  通过使用聚合物支持的脂肪酶，研究了一锅环保的ω-3脂肪酸乙酯向酰胺和单或二酰基甘油的氨基转移。该方法用于合成脂肪酸单甘油酯和酰胺的文库。发现这些新的衍生物对A549肺癌细胞具有有效的生长抑制作用。
• Synthesis and discovery of ω-3 polyunsaturated fatty acid- alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77
  作者：Hua Fang、Jianyu Zhang、Mingtao Ao、Fengming He、Weizhu Chen、Yuqing Qian、Yuxiang Zhang、Yang Xu、Meijuan Fang

  DOI：10.1016/j.bioorg.2020.104456

  日期：2020.12

  In this work, three series of ω-3 polyunsaturated fatty acid-alkanolamine derivatives (PUFA-AAs) were synthesized, characterized and their anti-inflammatory activity in vivo was evaluated. Compounds 4a, 4f, and 4k exhibited marked anti-inflammatory activity in LPS-stimulated RAW 264.7 cells. The most promising compound 4k dose-dependently suppressed the cytokines with IC₅₀ values in the low micromolar range. Further, 4k exhibited potential in vitro Nur77-binding affinity (K_d = 6.99 × 10^-6 M) which is consistent with the result of docking studies. Next, the anti-inflammatory mechanism of 4k was found to be through NF-κB signal pathway in a Nur77-dependent manner. Moreover, we also observed 4k significantly inhibited LPS-induced expression of cytokines (IL-6, TNF-α, and IL-1β) through suppressing NF-κB activation and attenuated LPS-induced inflammation in mouse acute lung injury (ALI) model. In conclusion, the study strongly suggests that the PUFA-AA derivatives can be particularly as new Nur77 mediators for further treatment in inflammatory diseases.