N-benzylicosa-5Z,8Z,11Z,14Z-tetraenamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-benzylicosa-5Z,8Z,11Z,14Z-tetraenamide
• 英文别名: (5Z,8Z,11Z,14Z)-N-benzylicosa-5,8,11,14-tetraenamide
• 化学式: C₂₇H₃₉NO
• 分子量: 393.613
• InChiKey: MGVDDEZGYMHBRC-DOFZRALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  29
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  Icosa-5,8,11,14-tetraynoic acid benzylamide 在 nickel diacetate sodium tetrahydroborate 、 氢气 、 乙二胺 作用下， 以 乙醇 为溶剂， 以21%的产率得到N-benzylicosa-5Z,8Z,11Z,14Z-tetraenamide
  参考文献：
  名称：

  Solid-Phase Synthesis of Anandamide Analogues

  摘要：

  The endocannabinoids are amides and esters of arachidonic acid that can mimic the pharmacological properties of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Anandamide, the most prominent of the endocannabinoids, has been implicated in both metabolic/physiological roles of the central nervous system, making it an attractive medicinal target. As such, we report the first solid-phase methodology that expedites access to various anandamide analogues. Our synthesis features a repetitive Cu-mediated coupling reaction between terminal alkynes and propargyl halides or allylic halides.

  DOI：

  10.1021/ol049474j

文献信息

• <i>N</i>-Benzyl-linoleamide, a Constituent of <i>Lepidium meyenii</i> (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain
  作者：Nalin Singh、Bogdan Barnych、Christophe Morisseau、Karen M. Wagner、Debin Wan、Ashley Takeshita、Hoang Pham、Ting Xu、Abhaya Dandekar、Jun-Yan Liu、Bruce D. Hammock

  DOI：10.1021/acs.jnatprod.0c00938

  日期：2020.12.24

  Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC₅₀ ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC₅₀ ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.
• A METHOD FOR TREATING PERIPHERAL INFLAMMATORY DISEASE
  申请人：Dublin City University

  公开号：EP3297621A1

  公开（公告）日：2018-03-28
• [EN] A METHOD FOR TREATING PERIPHERAL INFLAMMATORY DISEASE<br/>[FR] PROCÉDÉ DE TRAITEMENT D'UNE MALADIE INFLAMMATOIRE PÉRIPHÉRIQUE
  申请人：UNIV DUBLIN CITY

  公开号：WO2016185025A1

  公开（公告）日：2016-11-24

  An active for use in the treatment or inhibition of an inflammatory disease associated with over- activation of Toll-like Receptor 4 (TLR4), Toll-like Receptor 2 (TLR2) and Myeloid differentiating protein 88 (Myd88) adaptor-like protein (Ma1) while maintaining a subject's ability to respond normally to a pathogen, in which the active is an oleamide or an immunomodulatory analogue thereof.
• AM404 Analogs as Activators of the 20S Isoform of the Human Proteasome
  作者：Andres Salazar、Kate Kragness、Diogo Feleciano、Darci Jones Trader

  DOI：10.1002/cbic.202400284

  日期：——

  The proteasome is a multisubunit protease system responsible for the majority of the protein turnover in eukaryotic organisms. Dysregulation of this enzymatic complex leads to protein accumulation, subsequent aggregation, and ultimately diseased states; for that reason, positive modulation of its activity has been recently investigated as a therapeutic strategy for neurodegenerative and age‐related diseases. The small molecule AM404 was recently identified as an activator of the 20S isoform of the proteasome and further exploration of the scaffold revealed the importance of the polyunsaturated fatty acid chain to elicit activity. Herein, we report the investigation of the aromatic region of the scaffold and the evaluation of the small molecules in a variety of proteasome activity and protein degradation assays. We found that derivatives A22 and A23, compared to AM404, exhibit enhanced proteasome activity in biochemical and cellular proteasome assays and more favorable cellular viability profiles. Additionally, these compounds demonstrate the ability to degrade intrinsically disordered proteins, regardless of their molecular weight, and the ability to restore the proteasome activity in the presence of toxic oligomeric α‐Syn species in a biochemical setting.
• Solid-Phase Synthesis of Anandamide Analogues
  作者：Longwu Qi、Michael M. Meijler、Sang-Hyeup Lee、Chengzao Sun、Kim D. Janda

  DOI：10.1021/ol049474j

  日期：2004.5.1

  The endocannabinoids are amides and esters of arachidonic acid that can mimic the pharmacological properties of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Anandamide, the most prominent of the endocannabinoids, has been implicated in both metabolic/physiological roles of the central nervous system, making it an attractive medicinal target. As such, we report the first solid-phase methodology that expedites access to various anandamide analogues. Our synthesis features a repetitive Cu-mediated coupling reaction between terminal alkynes and propargyl halides or allylic halides.