N-Linolenoyldopamine | 105955-13-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-Linolenoyldopamine
• 英文别名: (Z,Z,Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]-octadeca-9,12,15-trienamide；(9Z,12Z,15Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]octadeca-9,12,15-trienamide
• CAS: 105955-13-3
• 化学式: C₂₆H₃₉NO₃
• 分子量: 413.601
• InChiKey: WKASWGQDAKPOAS-PDBXOOCHSA-N

物化性质

• 沸点：
  621.1±55.0 °C(Predicted)
• 密度：
  1.026±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  30
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  Γ-十八碳三烯酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-Linolenoyldopamine
  参考文献：
  名称：

  N-二十二碳六烯酰基，3羟基酪胺：一种多巴胺能化合物，可穿透血脑屏障并抑制食欲。

  摘要：

  具有可变链长（2-22个碳原子长）和不饱和度（0-6个双键）的脂肪酸用于合成多巴胺能化合物，以研究载体介导的多巴胺（DA）向大脑的转运。活性最高的载体是全顺式C22：6脂肪酸[二十二碳六烯酸（DHA）]，它通过血脑屏障的DA摄取增加了7.5倍以上。DHA-DA化合物NMI 8739以剂量依赖性方式抑制了小鼠的总体运动活性。它还以10 mg / kg的剂量分别抑制Balb c小鼠和Charles River大鼠的食欲50％和95％。连续三周每日服用NMI-8739不会引起耐受性。这些结果证明了DHA在载体介导的小分子向大脑转运方面的潜力。

  DOI：

  10.1016/0024-3205(96)00101-4

文献信息

• Inhibition of in Vitro Prostaglandin and Leukotriene Biosyntheses by Cinnamoyl-.BETA.-phenethylamine and N-Acyldopamine Derivatives.
  作者：Chen-Fang TSENG、Satoshi IWAKAMI、Akihiro MIKAJIRI、Masaaki SHIBUYA、Fumio HANAOKA、Yutaka EBIZUKA、Kosashi PADMAWINATA、Ushio SANKAWA

  DOI：10.1248/cpb.40.396

  日期：——

  N-trans- and N-cis-Feruloyltyramines were isolated as the inhibitors of in vitro prostaglandin (PG) synthesis from an Indonesian medicinal plant, Ipomoea aquatica (Convolvulaceae). In order to clarify structure activity relationships, cinnamoyl-β-phenethylamines with possible combinations of naturally occurring cinnamic acids and β-phenethylamines were synthesized and tested for their inhibitory activities against PG synthetase and arachidonate 5-lipoxygenase. The compounds containing catechol groups such as N-caffeoyl-β-phenethylamine (CaP) showed higher inhibitory effects on PG synthetase. The catechol group was found to be essential for the inhibition of arachidonate 5-lipoxygenase. The investigation of concentration dependent effects on PG biosynthesis revealed that CaP enhanced PG biosynthesis at a lower concentration range, whereas it inhibited the reaction at a higher concentration. The effects of CaP on each reaction step were investigated with purified PG endoperoxide synthase and microsomal PG synthetase. CaP inhibited the cyclooxygenase reaction, while it enhanced the hydroperoxidase reaction. N-Acyldopamines which contain catechol and lipophylic group were synthesized from dopamine and fatty acids to test their inhibitory effects on arachidonate 5-lipoxygenase. N-Linoleoyldopamine was the most active compound and its IC50 value was 2.3nM in our assay system, in which an IC50 value of AA 861, a specific inhibitor of 5-lipoxygenase, was 8nM.

  N-反式和N-顺式-阿魏酰基酪胺是从印尼药用植物空心菜（旋花科）中分离得到的体外前列腺素（PG）合成抑制剂。为了阐明结构活性关系，合成了可能由天然存在的肉桂酸和β-苯乙胺组合得到的肉桂酰-β-苯乙胺，并测试了它们对PG合成酶和花生四烯酸5-脂氧合酶的抑制活性。含有儿茶酚基团的化合物，如N-咖啡酰基-β-苯乙胺（CaP），显示出对PG合成酶更高的抑制效果。儿茶酚基团被发现对抑制花生四烯酸5-脂氧合酶至关重要。对浓度依赖性PG生物合成效应的研究表明，CaP在较低浓度范围内增强了PG生物合成，而在较高浓度下抑制了反应。通过纯化的PG内过氧化物合成酶和微粒体PG合成酶研究了CaP对每个反应步骤的影响。CaP抑制了环氧合酶反应，同时增强了氢过氧化物酶反应。从多巴胺和脂肪酸合成了含有儿茶酚和脂溶性基团的N-酰基多巴胺，以测试它们对花生四烯酸5-脂氧合酶的抑制效果。N-亚油酰多巴胺是最活跃的化合物，在我们的测定系统中其IC50值为2.3nM，而作为5-脂氧合酶特异性抑制剂的AA 861的IC50值为8nM。
• Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine
  作者：Vladimir Bezuglov、Mikhail Bobrov、Natalia Gretskaya、Alla Gonchar、Galina Zinchenko、Dominique Melck、Tiziana Bisogno、Vincenzo Di Marzo、Dmitry Kuklev、Jean-Claude Rossi、Jean-Pierre Vidal、Thierry Durand

  DOI：10.1016/s0960-894x(00)00689-2

  日期：2001.2

  amides of different fatty acids from the C18, C20, and C22 series with dopamine were synthesized. Pharmacological characterization in binding assays with rat brain membrane preparations and in the 'tetrad' of cannabinoid behavioral tests showed that, for these compounds, cannabinoid-like activity was dependent on the fatty acid moiety. Our data demonstrate that polyenoic fatty acid amides with dopamine

  合成了来自C18，C20和C22系列的不同脂肪酸的新酰胺与多巴胺。用大鼠脑膜制剂进行的结合试验以及大麻素行为测试的“四联体”中的药理学表征表明，对于这些化合物，类似大麻素的活性取决于脂肪酸部分。我们的数据表明，多巴胺的多烯脂肪酸酰胺构成了合成大麻素的新家族。
• Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads
  作者：Hung The Dang、Gyeoung Jin Kang、Eun Sook Yoo、Jongki Hong、Jae Sue Choi、Hyung Sik Kim、Hae Young Chung、Jee H. Jung

  DOI：10.1016/j.bmc.2010.12.046

  日期：2011.2

  A series of endogenous fatty acid amides and their analogues (1-78) were prepared, and their inhibitory effects on pro-inflammatory mediators (NO, IL-1 beta, IL-6, and TNF-alpha) in LPS-activated RAW264.7 cells were evaluated. Their inhibitory activity on the pro-inflammatory chemokine MDC in IFN-gamma-activated HaCaT cells was also examined. The results showed that the activity is strongly dependent on the nature of the fatty acid part of the molecules. As expected, the amides derived from enone fatty acids showed significant activity and were more active than those derived from other types of fatty acids. A variation of the amine headgroup also altered bioactivity profile remarkably, possibly by modulating cell permeability. Regarding the amine part of the molecules, N-acyl dopamines exhibited the most potent activity (IC50 similar to 2 mu M). This is the first report of the inhibitory activity of endogenous fatty acid amides and their analogues on the production of nitric oxide, cytokines (IL-1 beta, IL-6, and TNF-alpha) and the chemokine MDC. This study suggests that the enone fatty acid-derived amides (such as N-acyl ethanolamines and N-acyl amino acids) and N-acyl dopamines may be potential anti-inflammatory leads. (C) 2010 Elsevier Ltd. All rights reserved.
• HIGHLY EFFICIENT SYNTHESIS OF FATTY ACID DOPAMIDES
  作者：Z. Czarnocki、M. P. Matuszewska、I. Matuszewska

  DOI：10.1080/00304949809355327

  日期：1998.12
• MIKAVA, USIO
  作者：MIKAVA, USIO

  DOI：——

  日期：——