(4Z,7Z,10Z,13Z,16Z,19Z)-N-(3,4-dihydroxyphenethyl)docosa-4,7,10,13,16,19-hexaenamide | 129024-87-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (4Z,7Z,10Z,13Z,16Z,19Z)-N-(3,4-dihydroxyphenethyl)docosa-4,7,10,13,16,19-hexaenamide
• 英文别名: (Z,Z,Z,Z,Z,Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]-docosa-4,7,10,13,16,19-hexaenamide；N-docosahexaenoyl dopamine；docosahexaenoyldopamine；NMI-8739；DHA-DA；DHDA；Dha-DA conjugate；(4Z,7Z,10Z,13Z,16Z,19Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]docosa-4,7,10,13,16,19-hexaenamide
• CAS: 129024-87-9
• 化学式: C₃₀H₄₁NO₃
• 分子量: 463.66
• InChiKey: HXJMZRVSTICUKC-KUBAVDMBSA-N

物化性质

• 沸点：
  659.2±55.0 °C(Predicted)
• 密度：
  1.030±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：可混溶； DMSO：可混溶；乙醇：可混溶；乙醇:PBS(pH 7.2) (1:1): .1 mg/ml 胶体悬浮液

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  34
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，干燥环境

制备方法与用途

NMI 8739 是一种多巴胺 D2 自受体激动剂，同时也是多巴胺载体及神经递质多巴胺的氨基结合物。

反应信息

• 作为反应物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 (4Z,7Z,10Z,13Z,16Z,19Z)-N-(3,4-dihydroxyphenethyl)docosa-4,7,10,13,16,19-hexaenamide 、 4-氨基丁酸 在 三乙胺 作用下， 以 乙腈 、 水 为溶剂， 反应 19.75h， 以53%的产率得到
  参考文献：
  名称：

  Differences Between Cerebrovascular and Anti-Ischemic Effects of Dopamine, Docosahexaenoyldopamine, and GABA–Docosahexaenoyldopamine Conjugate

  摘要：

  多巴胺、合成物质二十二碳六烯酰多巴胺（DHA-DA）及其与GABA的共轭物（OXL1220）的脑血管和抗缺血效应进行了比较，发现它们存在差异。多巴胺和DHA-DA增加了完整及缺血大脑的血流量，这与显著的高血压反应相关。后者抑制多巴胺转运体的IC50为29微摩尔，但在作为多巴胺受体的配体方面几乎无效。OXL1220对经历短暂全脑缺血的大脑血流产生了选择性的血管舒张效应。仅有OXL1220能在体外与大鼠大脑GABAA受体上的[3H]加巴喷丁特异性结合位点竞争。因此，将神经递质GABA与DHA-DA结合，改变了该化合物在缺血大脑中对血管张力的多巴胺能活性，转变为GABA能活性。

  DOI：

  10.1007/s11094-016-1348-7
• 作为产物：
  描述：

  N-(3,4-dihydroxyphenethyl)phthalimide 在 对甲苯磺酸 三氟乙酸 、 肼 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 、 苯 为溶剂， 反应 149.0h， 生成 (4Z,7Z,10Z,13Z,16Z,19Z)-N-(3,4-dihydroxyphenethyl)docosa-4,7,10,13,16,19-hexaenamide
  参考文献：
  名称：

  Method of synthesizing acetonide-protected catechol-containing compounds and intermediates produced therein

  摘要：

  发明者在这里披露了一种新颖、简便的合成含有至少一个胺基的丙酮酸酯保护的邻苯二酚化合物的方法。在具体实施方案中，该发明提供了合成3,4-二羟基苯丙氨酸（H-DOPA(acetonide)-OH (6)）、Fmoc保护的H-DOPA(acetonide)-OH (Fmoc-DOPA(acetonide)-OH (7)）、Fmoc保护的多巴胺（Fmoc-dopamine(acetonide) (10)）、TFA保护的多巴胺（TFA-dopamine(acetonide) (13)）和丙酮酯保护的4-(2-氨基乙基)苯1,2-二酚（丙酮酯保护的多巴胺 (14)）的新方法。

  公开号：

  US08227628B2

文献信息

• N-docosahexaenoyl, 3 hydroxytyramine : A dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite
  作者：Victor E. Shashoua、Gary W. Hesse

  DOI：10.1016/0024-3205(96)00101-4

  日期：1996.3

  unsaturation (0-6 double bonds) were used to synthesize dopaminergic compounds for a study of the carrier mediated transport of dopamine (DA) to the brain. The most active carrier was the all cis C22:6 fatty acid [docosahexaenoic acid, (DHA)]which increased DA uptake through the blood-brain barrier by greater than 7.5 fold. The DHA-DA compound, NMI 8739, depressed the general locomotor activity of mice

  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。
• 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。
• Structure–Activity Relationships of Fish Oil Derivatives with Antiallergic Activity in Vitro and in Vivo
  作者：In-Hae Kim、Yoshiki Kanayama、Hisashi Nishiwaki、Takuya Sugahara、Kosuke Nishi

  DOI：10.1021/acs.jmedchem.9b00994

  日期：2019.11.14

  antiallergic activity in vitro. Ethanolamides of omega-3 fatty acids (α-linolenic acid, EPA, and DHA) were found to possess promising antiallergic activity, whereas free fatty acids and ethanolamides of other fatty acids exhibited no or weak potency. Based on this finding, structure–activity relationships of DHA-ethanolamide (DHEA) derivatives were investigated to yield better fatty acid derivatives with enhanced

  探索了鱼油中的一系列不饱和脂肪酸及其相应的乙醇酰胺代谢物，以发现具有抗过敏活性的活性鱼油成分。发现ω-3脂肪酸的乙醇酰胺（α-亚麻酸，EPA和DHA）具有良好的抗过敏活性，而游离脂肪酸和其他脂肪酸的乙醇酰胺则没有或表现出弱的功效。基于这一发现，研究了DHA-乙醇酰胺（DHEA）衍生物的结构-活性关系，以在体内和体外产生具有增强的抗过敏活性的更好的脂肪酸衍生物。当DHEA的乙醇酰胺部分被取代的磺酰胺官能团取代时，在体外提供了非常有前途的效价。化合物59在体内显示出比DHEA更高的抗过敏活性。结果表明，优化的DHEA衍生物在体内和体外具有增强的抗过敏活性，并且所得结构将成为进一步开发具有良好抗过敏活性的生物利用性衍生物的重要基础。
• Method of Synthesizing Acetonide-Protected Catechol-Containing Compounds and Intermediates Produced Therein
  申请人：Messersmith Phillip B.

  公开号：US20100087622A1

  公开（公告）日：2010-04-08

  The inventors disclose here a novel, facile approach to the synthesis of acetonide-protected catechol-containing compounds having at least one amine group. In specific embodiments, the invention provides novel methods of synthesizing 3,4-dihydroxyphenylalanine (H-DOPA(acetonide)-OH (6)), Fmoc-protected H-DOPA(acetonide)-OH (Fmoc-DOPA(acetonide)-OH (7)), Fmoc-protected dopamine (Fmoc-dopamine(acetonide) (10)), TFA-protected dopamine (TFA-dopamine(acetonide) (13)) and acetonide-protected 4-(2-aminoethyl)benzene-1,2-diol (acetonide-protected dopamine (14)).

  本发明披露了一种新颖、简便的方法，用于合成至少含有一个胺基的丙酮糖保护的儿茶酚类化合物。在具体实施中，本发明提供了合成3,4-二羟基苯丙氨酸（H-DOPA（丙酮糖）-OH（6））、Fmoc-保护的H-DOPA（丙酮糖）-OH（Fmoc-DOPA（丙酮糖）-OH（7））、Fmoc-保护的多巴胺（Fmoc-多巴胺（丙酮糖）（10））、TFA-保护的多巴胺（TFA-多巴胺（丙酮糖）（13））和丙酮糖保护的4-（2-氨基乙基）苯-1,2-二酚（丙酮糖保护的多巴胺（14））的新方法。
• 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.