N-阿魏酰基血清素 | 68573-23-9

• 物质功能分类: 原料药 - 抗肿瘤药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: N-阿魏酰基血清素
• 英文名称: N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamide
• 英文别名: N-feruloyl-5-hydroxytryptamine；N-feruloyl serotonin；N-feruloylserotonin；feruloylserotonin；moschamine；N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)-2-propenamide；N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide
• CAS: 68573-23-9
• 化学式: C₂₀H₂₀N₂O₄
• 分子量: 352.39
• InChiKey: WGHKJYWENWLOMY-UHFFFAOYSA-N

物化性质

• 熔点：
  110-114 °C
• 沸点：
  705.6±60.0 °C(Predicted)
• 密度：
  1.338±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 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：
  94.6
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 储存条件：
  存储条件：2-8°C，密封于干燥环境中。

制备方法与用途

应用

N-阿魏羟色胺具有抗炎、抗肿瘤及抑菌的作用，在红花等药用植物中存在微量。由于药用资源有限，开发其新的来源变得尤为重要。红花籽中含有约0.5%的苯丙烯酰5-羟色胺化合物，目前已发现了7至8种，其中N-阿魏羟色胺和N-(p-香豆酰)5-羟色胺最为常见。这两种化合物具有较强的清除自由基及抗脂质过氧化作用、抗肿瘤活性、抗炎抑菌作用以及抑制黑色素生成的功能，广泛应用于食品、药品、化妆品、工程树脂等领域。

生物活性

N-Feruloylserotonin 是从红花（Carthamus tinctorius L.）中分离得到的一种血清素衍生物，具有显著的抗氧化活性，并在动脉粥样硬化和主动脉壁膨胀的研究中有潜在的应用价值。

反应信息

• 作为产物：
  描述：

  5-羟基色胺 、 ferulic acid anhydride 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 N-阿魏酰基血清素
  参考文献：
  名称：

  Synthesis, biological activities and bioavailability of moschamine, a safflomide-type phenylpropenoic acid amide found inCentaurea cyanus

  摘要：

  Moschamine is a phenylpropenoic acid amide found in plants. In this article, the synthesis and two biological activities (serotoninergic and cyclooxygenase (COX) inhibitory activities) and bioavailability of moschamine were described. Moschamine was synthesised and confirmed using NMR spectroscopic methods. Using the moschamine synthesised, serotoninergic and COX inhibitory activities were investigated. At the concentration of 10 mu mol L-1, moschamine was able to inhibit forskolin-stimulated cAMP formation by 25% (p < 0.015), via inhibiting serotonin receptors in the OK cells. The inhibition was repressed by two 5-HT1 antagonists (Nan-190 and spiperone), suggesting that moschamine may suppress cAMP formation via binding to 5-HT1 receptors in the cells. Also, moschamine was a very potent compound that is able to inhibit COX-I by 58% (p < 0.012) and COX-II by 54% (p < 0.014), at the concentration of 0.1 mu mol L-1. The oral bioavailability of moschamine was also determined in mice.

  DOI：

  10.1080/14786419.2011.562207

文献信息

• Total Synthesis of (+)- and (−)-Decursivine and (±)-Serotobenine through a Cascade Witkop Photocyclization/Elimination/Addition Sequence: Scope and Mechanistic Insights
  作者：Weimin Hu、Hua Qin、Yuxin Cui、Yanxing Jia

  DOI：10.1002/chem.201204137

  日期：2013.2.25

  synthesis of not only racemic decursivine and serotobenine, but also enantiopure (+)‐ and (−)‐decursivine and a variety of their analogues. The present syntheses represent the shortest pathway for the total synthesis of decursivine and serotobenine to date. Moreover, the newly developed cascade sequence for the total synthesis of decursivine does not need any protecting steps. The scope and the reaction

  在本文中，介绍了抗疟疾化合物去甲锡藤及其生物学上无活性的同型血清素的总合成方法。首先研究了（±）-serotobenine的仿生合成，但没有成功。在随后的其他合成路线研究中，我们发现了新的级联Witkop光环化/消除/加成序列，该序列不仅能使外消旋的十碳体和血清型贝宁，而且对映体（+）-和（-）-十碳体和一个对映体纯合子的合成成为可能。各种各样的类似物。目前的合成方法代表了迄今为止全合成十倍体藤黄素和血清素联苯胺的最短途径。而且，新开发的用于癸二烯全合成的级联序列不需要任何保护步骤。还研究了级联序列的范围和反应机理。
• Serotonin derivatives as inhibitors of -secretase (BACE 1)
  作者：Takahashi、Miyazawa, Mitsuo

  DOI：10.1691/ph.2011.0789

  日期：——

  All serotonin derivatives described here (1–9) inhibited BACE 1 in a dose dependent manner. The 50% Inhibition Concentration (IC50 ) of N -cinnamoyl serotonin (1) was 86.7 ± 4.0 M. The peptide conjugation of serotonin derivatives influenced the BACE 1 inhibitory activity. Among serotonin derivatives (1–8), introduction of substituents, such as hydroxyl and methoxy groups at the 4 -position decreased the inhibitory activity (N - p -coumaroyl serotonin (2), N - p -methoxy cinnamoyl serotonin (3)). With a hydroxylgroup at the 4 -position, and the meta -hydroxy function being substituted by a hydroxyl group or methoxy group ( N caffeoyl serotonin (4), N -feruloyl serotonin (5)), inhibitory activity was weakened, (IC50 > 400 M). BACE 1 inhibitory activity was effected by the substituents of the cinnamic acid moiety. This is the first report on Structure-Activity-Relationships (SAR) for the BACE 1-inhibiting activity of serotonin derivatives. These serotonin derivatives, which have anti-oxidative effects as well are expected to be useful in the study of the mechanisms of Alzheimer's disease.

  这里描述的所有血清素衍生物 (1-9) 均以剂量依赖性方式抑制 BACE 1。 N-肉桂酰血清素 (1) 的 50% 抑制浓度 (IC50) 为 86.7 ± 4.0 M。血清素衍生物的肽缀合影响 BACE 1 抑制活性。在血清素衍生物 (1–8) 中，4 位羟基和甲氧基等取代基的引入降低了抑制活性（N - 对香豆酰血清素 (2)、N - 对甲氧基肉桂酰血清素 (3)） 。 4位有羟基，间位羟基被羟基或甲氧基取代（N咖啡酰血清素（4）、N-阿魏酰血清素（5）），抑制活性减弱，（IC50>400）米）。 BACE 1 抑制活性受肉桂酸部分的取代基影响。这是第一份关于血清素衍生物 BACE 1 抑制活性的结构-活性-关系 (SAR) 的报告。这些血清素衍生物也具有抗氧化作用，预计可用于阿尔茨海默病机制的研究。
• Facile Amidation of Non-Protected Hydroxycinnamic Acids for the Synthesis of Natural Phenol Amides
  作者：Annemiek van Zadelhoff、Jean-Paul Vincken、Wouter J. C. de Bruijn

  DOI：10.3390/molecules27072203

  日期：——

  to develop a facile general synthetic route to obtain phenol amides with a wide structural diversity. The result is a protocol for straightforward one-pot synthesis of phenol amides at room temperature within 25 h using equimolar amounts of N,N′-dicyclohexylcarbodiimide (DCC), amine, hydroxycinnamic acid, and sodium bicarbonate in aqueous acetone. Eight structurally diverse phenol amides were synthesized

  酚酰胺是许多植物中天然存在的生物活性化合物。这类化合物以抗氧化、抗炎和抗癌活性而闻名。为了更好地了解酚酰胺的反应性和结构-生物活性关系，需要大量结构多样的纯化合物，但从植物中纯化效率低且费力。现有的合成需要多个步骤，包括保护官能团，通常过于复杂，仅适用于羟基肉桂酸和胺的特定组合。因此，为了促进对这些有前途的化合物的进一步研究，我们旨在开发一种简便的通用合成路线来获得具有广泛结构多样性的酚酰胺。N , N '-二环己基碳二亚胺 (DCC)、胺、羟基肉桂酸和碳酸氢钠在丙酮水溶液中。合成了八种结构多样的酚酰胺并对其进行了充分的化学表征。本工作中描述的简便合成路线适用于多种生物相关的酚酰胺，由不同的羟基肉桂酸亚基（香豆酸、阿魏酸和芥子酸）和胺亚基（胍丁胺、邻氨基苯甲酸、腐胺、血清素、酪胺和色胺），产率在 14% 和 24% 之间。
• Synthesis and structure–activity relationships of phenylpropanoid amides of serotonin on tyrosinase inhibition
  作者：Toshiyuki Takahashi、Mitsuo Miyazawa

  DOI：10.1016/j.bmcl.2011.02.028

  日期：2011.4

  In this manuscript, we synthesized a series of phenylpropanoid amide of serotonin 1-9, analyzed their structural importance for two biologic activities (antioxidant activity and tyrosinase inhibitory activity). While the serotonin moiety and the amide linkage of serotonin derivatives affect antioxidant activity strongly, the serotonin moiety, the amide linkage and the cinnamic acid moiety affect tyrosinase inhibitory activity. Among tested compounds, compound 4 which contains cathechol moiety exhibited the most antioxidant activity (EC50 = 19.4 +/- 2.0 mu M), and compound 6 exhibited significant tyrosinase inhibitory activity (IC50 = 5.4 +/- 3.6 mu M). Our data suggests that a useful clue for the design and development of new tyrosinase inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of serotonin derivatives effect on α-glucosidase inhibition
  作者：Toshiyuki Takahashi、Mitsuo Miyazawa

  DOI：10.1007/s00044-011-9699-9

  日期：2012.8

  The alpha-glucosidase inhibitory activities of serotonin derivatives were evaluated. Two serotonin derivatives, N-p-coumaroyl serotonin (2) and N-caffeoyl serotonin (4) exhibited most potent inhibition on alpha-glucosidase, whereas, cinnamic acid derivatives were less efficient. Furthermore, we analyzed their structural importance for alpha-glucosidase inhibition. The linkage of cinnamic acid moiety and serotonin moiety and the olefin in cinnamic acid moiety of serotonin derivatives were crucial for alpha-glucosidase inhibition. This is the first report on structure-activity relationships (SAR) for the alpha-glucosidase inhibitory activity of serotonin derivatives.