O-(2-氨基乙基)-5Z,8Z,11Z,14Z-二十碳四烯酸酯 | 287937-12-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: O-(2-氨基乙基)-5Z,8Z,11Z,14Z-二十碳四烯酸酯
• 英文名称: virodhamine
• 英文别名: O-arachidonoyl ethanolamine；2-aminoethyl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
• CAS: 287937-12-6
• 化学式: C₂₂H₃₇NO₂
• 分子量: 347.541
• InChiKey: DLHLOYYQQGSXCC-DOFZRALJSA-N

物化性质

• 沸点：
  450.3±45.0 °C(Predicted)
• 密度：
  0.930±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  25
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C

制备方法与用途

维罗达明是一种内源性大麻素，能够激活大麻素(CB)受体以调节神经传递。维拉帕米则是CB1受体的拮抗剂和CB2受体的激动剂。研究表明，维罗达明可通过触发MAPK信号通路及促进活性氧(ROS)生成来诱导巨核细胞分化。此外，这种化合物可用于研究多种神经系统疾病，如阿尔茨海默病和帕金森病等[1][2]。

反应信息

• 作为产物：
  描述：

  大麻素 在 盐酸 作用下， 以 水 为溶剂， 生成 O-(2-氨基乙基)-5Z,8Z,11Z,14Z-二十碳四烯酸酯
  参考文献：
  名称：

  Synthesis of all-trans anandamide: A substrate for fatty acid amide hydrolase with dual effects on rabbit platelet activation

  摘要：

  Anandamide (AEA) presents the four double bonds in the cis configuration, deriving from the arachidonic acid moiety. In the context of an antisense strategy based on the double bond configuration, all-trans AEA (t-AEA) was synthesized in high yield starting from all-trans methyl arachidonate and ethanolamine in the presence of KCN. t-AEA was assayed on rabbit platelet aggregation, obtaining effect only at high concentrations (> 10 (4) M) after an also concentration-dependent lag phase. At lower concentrations it inhibited PAF-induced rabbit platelet aggregation with an IC50 = 4.6 x 10 (6) M. In contrast to anandamide, the activation of platelets was not due to the conversion of t-AEA to trans arachidonic acid, as ascertained by negative results with FAAH inhibitors. However, t-AEA was found to be a substrate for fatty acid amide hydrolase (FAAH), the enzyme that cleaves anandamide and regulates in vivo the magnitude and duration of the signaling induced by this lipid messenger. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.08.054

文献信息

• [EN] NOVEL CANNABINOID RECEPTOR LIGANDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESS FOR THEIR PREPARATION<br/>[FR] NOUVEAUX LIGANDS DU RÉCEPTEUR CANNOBINOÏDE, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2009053799A1

  公开（公告）日：2009-04-30

  The present invention relates to compounds of f formula (I) as cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2 ) receptor modulators, and uses thereof f or treating diseases, conditions and/or disorders modulated by a cannabinoid receptor ( such as pain, neurodegenrative disorders, eating disorders, weight loss or control, and obesity).

  本发明涉及公式（I）的化合物作为大麻素受体调节剂，特别是大麻素1（CB1）或大麻素2（CB2）受体调节剂，以及它们的用途用于治疗由大麻素受体调节的疾病、症状和/或障碍（如疼痛、神经退行性疾病、进食障碍、体重减轻或控制以及肥胖症）。
• [EN] RADIOLABELED CANNABINOID-1 RECEPTOR MODULATORS<br/>[FR] MODULATEURS RADIOMARQUES DU RECEPTEUR DE CANNABINOIDE-1
  申请人：MERCK & CO INC

  公开号：WO2005009479A1

  公开（公告）日：2005-02-03

  The present invention relates to particular radiolabeled Cannabinoid-1 (CB1) receptor modulators, and methods of using these modulators for labeling and diagnostic imaging of Cannabinoid-1 receptors in mammals, particularly humans. In addition, intermediates useful for the synthesis of the radiolabeled Cannabinoid-1 receptor modulators are also disclosed, as well as the processes for synthesizing the radiolabeled Cannabinoid-1 receptor modulators. Still further, formulations of the radiolabeled Cannabinoid-1 receptor compounds are described.

  本发明涉及特定的放射标记的大麻素-1（CB1）受体调节剂，以及使用这些调节剂进行哺乳动物，特别是人类大麻素-1受体的标记和诊断成像的方法。此外，还公开了用于合成放射标记的大麻素-1受体调节剂的中间体，以及用于合成放射标记的大麻素-1受体调节剂的过程。此外，还描述了放射标记的大麻素-1受体化合物的配方。
• NOVEL CANNABINOID RECEPTOR LIGANDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESSES FOR THEIR PREPARATION
  申请人：Muthuppalaniappan Meyyappan

  公开号：US20080200501A1

  公开（公告）日：2008-08-21

  The present invention relates to novel cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and/or disorders modulated by a cannabinoid receptor (such as pain, neurodegenative disorders, eating disorders, weight loss or control, and obesity).

  本发明涉及新型大麻素受体调节剂，特别是大麻素1（CB1）或大麻素2（CB2）受体调节剂，以及它们用于治疗受大麻素受体调节的疾病、症状和/或紊乱（如疼痛、神经退行性疾病、进食紊乱、体重减轻或控制以及肥胖）的用途。
• GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation
  作者：Mikhail G. Akimov、Alina M. Gamisonia、Polina V. Dudina、Natalia M. Gretskaya、Anastasia A. Gaydaryova、Andrey S. Kuznetsov、Galina N. Zinchenko、Vladimir V. Bezuglov

  DOI：10.3390/ijms22020622

  日期：——

  GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca2+, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.

  GPR55是非CB1/CB2大麻素受体家族的G蛋白偶联受体，被赖氨磷脂酰肌醇(LPI)激活，刺激癌细胞增殖。阿南达胺是一种生物活性脂质内源大麻素，作为GPR55的有偏激动剂，并诱导癌细胞死亡，但不稳定且具有精神活性。我们假设其他内源大麻素和结构相似的化合物，其在水解稳定性方面更好，也可以通过激活GPR55诱导癌细胞死亡。我们化学合成并测试了一组脂肪酸酰胺和酯类化合物，通过激活GPR55诱导细胞死亡。最活跃的化合物似乎是N-酰多巴胺，特别是N-二十二碳六烯酰多巴胺（DHA-DA）。我们首次展示了对这些化合物，细胞死亡诱导机制与阿南达胺发表的机制不同，包括神经型一氧化氮合酶（nNOS）过度刺激伴随氧化应激诱导。DHA-DA与LPI的结合，通常刺激癌细胞增殖且在癌症环境中增加，对癌细胞具有增强的细胞毒性，表明具有治疗潜力。
• [EN] COMPOSITIONS CONTAINING CANNABINOID ANALOG CONJUGATES AND METHODS OF USE<br/>[FR] COMPOSITIONS CONTENANT DES CONJUGUÉS D'ANALOGUES CANNABINOÏDES ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：VYRIPHARM ENTPR LLC

  公开号：WO2019018536A1

  公开（公告）日：2019-01-24

  Provided here are compositions containing a conjugate of a label, a chelator, and a cannabinoid analog and methods for diagnosing, treating, or monitoring the progression of a cancer or a neurologic disorder using these compositions. Also provided here are methods of synthesizing these compositions and kits for delivery of these compositions as imaging and therapeutic agents.

  在这里提供了包含标签的共轭物、螯合剂和大麻素类似物的组合物，以及使用这些组合物诊断、治疗或监测癌症或神经系统疾病进展的方法。还提供了合成这些组合物的方法以及用于传递这些组合物作为成像和治疗剂的工具包。