(4Z,7Z,10Z,13Z,16Z,19Z)-N-(4-hydroxybutyl)docosa-4,7,10,13,16,19-hexaenamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (4Z,7Z,10Z,13Z,16Z,19Z)-N-(4-hydroxybutyl)docosa-4,7,10,13,16,19-hexaenamide
• 英文别名: cis-docosa-4,7,10,13,16,19-hexaenoic acid (4-hydroxy butyl)amide；docosahexaenoylbutanolamine；NCGC00248434-01
• 化学式: C₂₆H₄₁NO₂
• 分子量: 399.617
• InChiKey: USOHASFSJWTGPW-KUBAVDMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  29
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4Z,7Z,10Z,13Z,16Z,19Z)-N-(4-hydroxybutyl)docosa-4,7,10,13,16,19-hexaenamide 、 萘普生 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  一种二十二碳六烯酰酯衍生物及其制备方法和应用

  摘要：

  本发明公开了一种二十二碳六烯酰酯衍生物及其制备方法和应用，其结构式为其中，n为0‑4的整数，R为或本发明对小鼠巨噬细胞RAW264.7中由脂多糖LPS诱导的促炎性介质的mRNA表达具有一定的下调作用，以及下调一氧化氮NO的外分泌水平，同时，能够抑制促炎性细胞因子的蛋白表达。

  公开号：

  CN114853628A
• 作为产物：
  描述：

  4-氨基-1-丁醇 、 (4Z,7Z,10Z,13Z,16Z,19Z)-4,7,10,13,16,19-二十二碳六烯酸乙酯 以 neat (no solvent) 为溶剂， 反应 24.0h， 以63%的产率得到(4Z,7Z,10Z,13Z,16Z,19Z)-N-(4-hydroxybutyl)docosa-4,7,10,13,16,19-hexaenamide
  参考文献：
  名称：

  Synthesis and discovery of ω-3 polyunsaturated fatty acid- alkanolamine (PUFA-AA) derivatives as anti-inflammatory agents targeting Nur77

  摘要：

  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.

  DOI：

  10.1016/j.bioorg.2020.104456

文献信息

• [EN] DERIVATIVES OF DOCOSAHEXAENOYLETHANOLAMIDE AND USES THEREOF<br/>[FR] DÉRIVÉS DE DOCOSAHEXAÉNOYLÉTHANOLAMIDE ET SES UTILISATIONS
  申请人：US HEALTH

  公开号：WO2013158302A1

  公开（公告）日：2013-10-24

  The invention provides derivatives of DEA which have increased potency and hydrolysis resistance as compared to DEA, and compositions thereof, as well as methods of using these derivatives to promote neurogenesis, neurite growth and/or length, and/or promote synaptogenesis.

  本发明提供了与DEA相比具有更高效能和更强水解抗性的DEA衍生物及其组成物，以及使用这些衍生物促进神经发生、神经突起生长和/或长度，以及/或促进突触形成的方法。
• DERIVATIVES OF DOCOSAHEXAENOYLETHANOLAMIDE AND USES THEREOF
  申请人：The United States of America, as Represented by The Secretary, Department of Health and Human Services

  公开号：EP2847178B1

  公开（公告）日：2017-01-04
• US9422308B2
  申请人：——

  公开号：US9422308B2

  公开（公告）日：2016-08-23
• 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.
• 一种二十二碳六烯酰酯衍生物及其制备方法和应用
  申请人：自然资源部第三海洋研究所

  公开号：CN114853628A

  公开（公告）日：2022-08-05

  本发明公开了一种二十二碳六烯酰酯衍生物及其制备方法和应用，其结构式为其中，n为0‑4的整数，R为或本发明对小鼠巨噬细胞RAW264.7中由脂多糖LPS诱导的促炎性介质的mRNA表达具有一定的下调作用，以及下调一氧化氮NO的外分泌水平，同时，能够抑制促炎性细胞因子的蛋白表达。