2-propenamide, N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenyl-, (2E) | 456-12-2

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-propenamide, N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenyl-, (2E)
• 英文别名: N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenyl-2-propenamide；aegeline；(+/-)-N-(β-hydroxy-4-methoxy-phenethyl)-trans-cinnamamide；(+/-)-N-(β-Hydroxy-4-methoxy-phenaethyl)-trans-cinnamamid；Aegelin；(+/-)-N-Cinnamoyl-<2-hydroxy-2-(4'-methoxyphenyl)>ethylamin; Aegeline；(E)-N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenylprop-2-enamide
• CAS: 456-12-2
• 化学式: C₁₈H₁₉NO₃
• 分子量: 297.354
• InChiKey: QRFDENJATPJOKG-KPKJPENVSA-N

物化性质

• 熔点：
  178-179℃
• 沸点：
  567.7±50.0 °C(Predicted)
• 密度：
  1.178±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

毒理性

• 肝毒性

OxyELITE Pro 与至少50例临床上明显的急性肝损伤有关。损伤的发生通常在使用OxyELITE Pro常规剂量开始后2到20周内，或者改用OxyELITE Pro产品的改变配方之后。典型的表现症状是疲劳、恶心和腹痛，随后出现深色尿和黄疸。肝损伤的模式是肝细胞损伤，血清转氨酶水平升高到几千U/L，而碱性磷酸酶水平通常正常或轻微升高（不到正常上限的3倍）。肝脏活检显示急性肝炎样的图像，严重病例与融合性、亚大块或大块坏死相关。免疫过敏特征并不常见，但常常检测到自身抗体。实际上，一部分病例出现了类似自身免疫性肝炎的损伤模式，其中一些病例导致了慢性肝炎，并需要长期免疫抑制治疗，尽管及时停用了该药物。总体而言，黄疸病例的死亡率大约为10%。在非致命性病例中，症状在1到8周内缓解，实验室检测在两到三个月内恢复正常。

OxyELITE Pro has been associated with at least 50 instances of clinically apparent acute liver injury. The onset of injury was usually within 2 to 20 weeks of starting regular use or of switching to the altered formulation of OxyELITE Pro products. The typical presenting symptoms were fatigue, nausea, and abdominal pain followed by dark urine and jaundice. The pattern of liver injury was hepatocellular and serum aminotransferase levels ranged to as high as several thousand U/L while alkaline phosphatase levels tended to be normal or minimally elevated (less than 3 times ULN). Liver biopsies showed an acute hepatitis-like picture and severe cases were associated with confluent, submassive or massive necrosis. Immunoallergic and features were not common, but autoantibodies were often detected. Indeed, instances of an autoimmune hepatitis-like pattern of injury occurred in a proportion of cases, some of which led to a chronic hepatitis and required long term immune suppressive therapy despite prompt withdrawal of the agent. The mortality rate overall was approximately 10% among cases with jaundice. In non-fatal cases, symptoms resolved within 1 to 8 weeks and laboratory tests returned to normal by two to three months.

来源:LiverTox

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

制备方法与用途

用途

印枳碱是一种化合物，可以从生长在印度的Aegle marmelos树的叶子中提取。研究发现这种树的精油对21种细菌有效，且印枳碱具有抗肥胖作用。

用途

印枳碱为芳香类衍生物，可用作医药合成中间体。

生物活性

Aegeline 是一种主要生物碱，能够模拟酵母 SNARE 蛋白 Sec22p 抑制酵母 α-突触核蛋白和 Bax 毒性。Aegeline 还能恢复由 α-syn 或 Bax 表达引起的酵母细胞生长。

体外研究

Aegeline 还可防止表达更具毒性的 A53T α-突触核蛋白突变体的细胞增殖受阻。其通过抑制 ROS 水平增加、线粒体膜电位丢失和核 DNA 碎片化等特征，恢复了 α-synuclein 或 Bax 表达细胞中的细胞生长。此外，Aegeline 在抑制 RPMCs 中组胺释放方面表现出微弱的抑制作用，即使在由 thapsigargin 引起的组胺释放时仍然有效。

反应信息

• 作为反应物：
  描述：

  2-propenamide, N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenyl-, (2E) 在 chromium(VI) oxide 、 溶剂黄146 作用下， 生成 N-[2-(4-methoxyphenyl)-2-keto-ethyl]-cinnamamide
  参考文献：
  名称：

  315.爱琴林的结构

  摘要：

  DOI：

  10.1039/jr9580001580
• 作为产物：
  描述：

  (+)-(5S)-2-(trans-styryl)-5-(4-methoxyphenyl)-Δ2-oxazoline 在 水 作用下， 生成 2-propenamide, N-[2-hydroxy-2-(4-methoxyphenyl)ethyl]-3-phenyl-, (2E)
  参考文献：
  名称：

  Shahidine, a novel and highly labile oxazoline from Aegle marmelos: the parent compound of aegeline and related amides

  摘要：

  A rare alkaloid, shahidine (1), having an unstable oxazoline core has been isolated as a major constituent from the fresh leaves of Aegle marmelos. It is moisture-sensitive, and found to be the parent compound of aegeline and other amides, however. it is stable in dimethyl sulfoxide. Its structure was established by spectroscopic analysis. Biogenetically, oxazolines may be considered as the precursor of hydroxy amides and oxazoles found in plants. Shahidine (1) showed activity against a few Gram-positive bacteria. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.11.088

文献信息

• 一种N-[2-羟基-2-(4-甲氧基苯基)乙基]肉桂 酰胺的合成方法
  申请人：苏利制药科技江阴有限公司

  公开号：CN109180515B

  公开（公告）日：2021-04-06

  本发明提供一种N‑[2‑羟基‑2‑(4‑甲氧基苯基)乙基]肉桂酰胺的合成方法，所述方法是以对甲氧基苯乙酮为起始原料，经过氯代反应、叠氮化反应、还原缩合反应反应制得。本发明反应原料易得，反应过程操作简单，反应设备要求低，反应条件相对温和，收率、含量高，最终所得N‑[2‑羟基‑2‑(4‑甲氧基苯基)乙基]肉桂酰胺的HPLC液相纯度大于99%。
• Compositions and Methods for Affecting Mental State and Body Composition
  申请人：USPLABS. LLC

  公开号：US20140134283A1

  公开（公告）日：2014-05-15

  The invention discloses compositions, including nutritional products and dietary supplements, comprising aegeline, which is a compound that occurs naturally in the Bael plant. The invention also describes methods comprising the administration of aegeline to mammals. The methods result in increased mental stamina, focus, and energy level, improved mood, increased thermogenesis, increased libido, and anabolic effects and increased strength output and/or muscle mass. These effects can improve cognition, influence body composition, promote weight loss, and/or promote fitness and well-being. A novel method for the synthesis of aegeline is also provided.

  该发明披露了包括永利素的组合物，其中永利素是一种天然存在于木槿果植物中的化合物，这些组合物包括营养产品和膳食补充剂。该发明还描述了涉及将永利素用于哺乳动物的方法。这些方法导致了增加的精神耐力、专注力和能量水平，改善了情绪，增加了热能产生，增加了性欲，具有促进肌肉合成的作用以及增加了力量输出和/或肌肉质量。这些效应可以改善认知能力，影响体态构成，促进减重，以及促进健康和健身。该发明还提供了一种合成永利素的新方法。
• Simultaneous Determination of Aegeline and Six Coumarins from Different Parts of the Plant Aegle marmelos Using UHPLC-PDA-MS and Chiral Separation of Aegeline Enantiomers Using HPLC-ToF-MS
  作者：Bharathi Avula、Amar Chittiboyina、Yan-Hong Wang、Satyanarayanaraju Sagi、Vijayasankar Raman、Mei Wang、Ikhlas Khan

  DOI：10.1055/s-0042-103160

  日期：——

  A fast UHPLC-PDA method was developed for the simultaneous analysis of one alkaloid, aegeline, and six coumarins, viz., umbelliferone, scopoletin, marmesinin, 8-hydroxypsoralen, angelicin, and marmelosin, from the leaf, fruit, root, and bark of Aegle marmelos. The UHPLC method was validated for linearity, accuracy, repeatability, limits of detection and limits of quantification. The linearity range

  开发了一种快速 UHPLC-PDA 方法，用于同时分析叶、果实、根和树皮中的一种生物碱、aegeline 和 6 种香豆素，即伞形酮、东莨菪碱、marmesinin、8-羟基补骨脂素、当归素和 marmelosin Aegle 马梅洛斯。UHPLC 方法的线性度、准确度、重复性、检测限和定量限均经过验证。七种化合物的线性范围 (r(2) > 0.99) 为 0.5-250 µg/mL，七种化合物的检测限和定量限分别为 0.1 和 0.5 µg/mL，分别。开发的 UHPLC 方法简单、快速，特别适用于 A. marmelos 和商业膳食补充剂中香豆素和 aegeline 的质量控制分析。单四极杆质谱用于鉴定和确认来自不同植物部位和膳食补充剂的香豆素和 aegeline。此外，还开发了一种新的手性 HPLC-ToF-MS 方法来拆分 aegeline 对映异构体。通过应用这种手性方法，首次报道了来自
• Catalytic dehydrative amide bond formation using aqueous ammonia: synthesis of primary amides utilizing diboronic acid anhydride catalysis
  作者：Naoya Takahashi、Hinata Iwasawa、Tatsuhito Kinashi、Kazuishi Makino、Naoyuki Shimada

  DOI：10.1039/d3cc02071a

  日期：——

  Although aqueous ammonia is an inexpensive and readily available safe source of ammonia, there have been no successful studies on direct catalytic dehydrative amidations of carboxylic acids with aqueous ammonia. In this study, we report a catalytic methodology for the synthesis of primary amides through diboronic acid anhydride (DBAA)-catalyzed dehydrative condensation of carboxylic acids with aqueous

  尽管氨水是一种廉价且容易获得的安全氨源，但目前还没有关于羧酸与氨水的直接催化脱水酰胺化的成功研究。在这项研究中，我们报告了一种通过二硼酸酐 (DBAA) 催化羧酸与氨水作为胺底物的脱水缩合来合成伯酰胺的催化方法。
• Adityachaudhury; Chatterjee, Journal of the Indian Chemical Society, 1959, vol. 36, p. 585,587
  作者：Adityachaudhury、Chatterjee

  DOI：——

  日期：——