arachidonyl azide | 220556-79-6

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: arachidonyl azide
• 英文别名: (5Z,8Z,11Z,14Z)-1-azidoicosa-5,8,11,14-tetraene
• CAS: 220556-79-6
• 化学式: C₂₀H₃₃N₃
• 分子量: 315.502
• InChiKey: KWUWUHPXGBPGTG-DOFZRALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  14.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  arachidonyl azide 在 lithium aluminium tetrahydride 、 三甲基铝 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 9.33h， 生成 N-(3-hydroxypropionyl)arachidonylamide
  参考文献：
  名称：

  Novel Analogues of Arachidonylethanolamide (Anandamide):  Affinities for the CB1 and CB2 Cannabinoid Receptors and Metabolic Stability

  摘要：

  Several analogues of the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide) were synthesized and evaluated in order to study (a) the structural requirements for high-affinity binding to the CB1 and CB2 cannabinoid receptors and (b) their hydrolytic stability toward anandamide amidase. The series reported here was aimed at exploring structure-activity relationships (SAR) primarily with regard to stereoelectronic requirements of ethanolamido headgroup for interaction with the cannabinoid receptor active site. Receptor affinities, reported as K-i values, were obtained by a standard receptor binding assay using [H-3]CP-55,940 as the radioligand, while stability toward the amidase was evaluated by comparing the K-i of each analogue in the presence and absence of phenylmethanesulfonyl fluoride (PMSF), a serine protease blocker and inhibitor of anandamide amidase. Introduction of a methyl group in the 1'- and 2'-positions or substitution of the ethanolamido headgroup with a butylamido group gave analogues with vastly improved biochemical stability. This is accomplished in some cases with increased receptor affinity. Conversely, oxazolyl and methyloxazolyl headgroups led to low-affinity analogues. Substitution of the hydroxyl group with electronegative substituents such as fluoro, chloro, allyl, and propargyl groups significantly increased receptor affinity but did not influence the biochemical stability. The 2'-chloro analogue of anandamide was found to have the highest affinity for CB1. Additionally, reversing the positions of the carbonyl and NH in the amido group produces retro-anandamides possessing considerably higher metabolic stability. Replacement of the arachidonyl tail with oleyl or linoleyl results in analogues with low affinities for both receptors. All of the analogues in this study showed high selectivity for the CB1 receptor over the peripheral CB2 receptor. The most potent analogues were tested for their ability to stimulate the binding of [S-35]GTP gamma S to G-proteins and were shown to be potent cannabimimetic agonists. The results are discussed in terms of pharmacophoric features affecting receptor affinity and enzymatic stability.

  DOI：

  10.1021/jm970257g
• 作为产物：
  描述：

  花生四烯酸 在 lithium aluminium tetrahydride 、 sodium azide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 arachidonyl azide
  参考文献：
  名称：

  用于合成芳基氮并三唑光开关的偶氮乙炔

  摘要：

  我们报告了一种针对新型芳基氮并三唑光开关及其光物理特性的模块化方法。锂化 TIPS-乙炔与芳基重氮四氟硼酸盐的加成得到范围广泛的偶氮乙炔，构成了一类尚未开发的稳定中间体。原位脱硅瞬时导致末端芳基偶氮乙炔发生铜催化环加成反应 (CuAAC)，并产生多种有机叠氮化物。这些包括源自天然产物或药物的复杂分子，例如秋水仙碱、紫杉醇、达菲和花生四烯酸。芳基氮并三唑显示近定量光异构化和长热Z-半条命。使用该方法，我们首次介绍了联乙炔平台的设计和合成。它允许实施连续和面向多样性的方法，将两种不同的偶联物连接到一个常见的光开关偶氮三唑中的独立可寻址乙炔。这在几种光开关偶联物的合成中得到了展示，具有作为 photoPROTAC 和生物素偶联物的潜在应用。

  DOI：

  10.1021/jacs.1c06014

文献信息

• Cannabimimetic lipid amides as useful medications
  申请人：University of Connecticut

  公开号：US07161016B1

  公开（公告）日：2007-01-09

  Novel analogs of arachidonylethanolamide are presented which have higher affinities for the cannabinoid CB1 and/or CB2 receptor sites. Further, most of the analogs exhibit greater metabolic stability than arachidonylethanolamide. The improved receptor affinity and selectivity and/or greater metabolic stability make these analogs therapeutically useful as medications for relief of pain caused by cancer and nausea caused by chemotherapy, as well as for peripheral pain. The compounds may also be useful as oral and topical contraceptives, in suppression of the immune system, enhancement of appetite and in treatment of psychomotor disorders, multiple sclerosis and hypertension.

  新型的花生四烯酰乙醇胺类似物具有更高的亲和力，适用于大麻素CB1和/或CB2受体位点。此外，大多数类似物表现出比花生四烯酰乙醇胺更高的代谢稳定性。改善的受体亲和力和选择性和/或更高的代谢稳定性使这些类似物在作为药物用于缓解癌症引起的疼痛和化疗引起的恶心，以及外周疼痛方面具有治疗用途。这些化合物也可能用于口服和局部避孕药、免疫系统抑制、增强食欲以及治疗精神运动障碍、多发性硬化和高血压。
• Synthesis and pharmacological evaluation of sulfamide-based analogues of anandamide
  作者：Carolina Cano、Juan Antonio Páez、Pilar Goya、Antonia Serrano、Javier Pavón、Fernando Rodríguez de Fonseca、Margarita Suardíaz、María Isabel Martín

  DOI：10.1016/j.ejmech.2009.08.003

  日期：2009.12

  Arachidonyl and linoleyl sulfamide derivatives have been synthesized and their potential cannabimimetic properties evaluated in in vitro functional and binding assays. Replacement of the ethanolamide moiety of anandamide by –CH2NHSO2NH–R considerably reduces the CB1 receptor activity and only some of the compounds showed modest cannabinoid properties in binding assays. The new compounds were also tested

  已经合成了花生四烯酸和亚油基磺酰胺衍生物，并在体外功能和结合试验中评估了它们的潜在拟大麻特性。-CH 2 NHSO 2 NH-R取代an南酰胺的乙醇酰胺部分会大大降低CB1受体的活性，只有一些化合物在结合分析中显示适度的大麻素特性。还测试了新化合物作为FAAH酶的抑制剂，但没有活性。
• Synthesis of novel thiourethane analogs of neurolipins
  作者：N. M. Gretskaya、A. A. Druzhinina、M. Yu. Bobrov、V. V. Bezuglov

  DOI：10.1007/s10600-013-0566-4

  日期：2013.5

  Thiourethane analogs of anandamide and arachidonic acid amides with cyclopropylamine, dopamine, and serotonin that were capable of inhibiting hydrolysis of fatty-acid amides and interacting with cannabinoid receptor type 1 were synthesized for the first time.

  首次合成了酰胺的硫脲醇类类似物，包括大麻素和花生四烯酸酰胺，带有环丙胺、多巴胺和血清素，能够抑制脂肪酸酰胺的水解并与大麻素受体类型1相互作用。
• Inhibitors of the anandamide transporter
  申请人：Makriyannis Alexandros

  公开号：US20050020679A1

  公开（公告）日：2005-01-27

  Disclosed are compounds that are anandamide transport inhibitors and their pharmacological use.

  本发明涉及一种阿南胺运输抑制剂化合物及其药理学用途。
• INHIBITORS OF THE ANANDAMIDE TRANSPORTER
  申请人：University of Connecticut

  公开号：EP1632236A1

  公开（公告）日：2006-03-08

  Disclosed are compounds that are anandamide transport inhibitors and their pharmacological use.

  所公开的化合物是一种羊酰胺转运抑制剂及其药理用途。