16,16-dimethyl-docosa-5,8,11,14-all-cis-tetraenoic acid methyl ester | 195612-62-5

• 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: 16,16-dimethyl-docosa-5,8,11,14-all-cis-tetraenoic acid methyl ester
• 英文别名: methyl (5Z,8Z,11Z,14Z)-16,16-dimethyldocosa-5,8,11,14-tetraenoate
• CAS: 195612-62-5
• 化学式: C₂₅H₄₂O₂
• 分子量: 374.607
• InChiKey: YFIILSHAEPVSAA-RPHFINAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  27
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  16,16-dimethyl-docosa-5,8,11,14-all-cis-tetraenoic acid methyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 生成 (5Z,8Z,11Z,14Z)-16,16-Dimethyl-docosa-5,8,11,14-tetraen-1-ol
  参考文献：
  名称：

  Synthesis and CB1 receptor activities of dimethylheptyl derivatives of 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE)

  摘要：

  Results from a factor analysis and activity studies of commercially available endocannabinoid-type compounds set the starting point for the current study where dimethylheptyl (DMH) analogues of two endocannabinoids, 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE), were synthesized and their ability to activate the CB1 receptors was determined by the [S-35]GTP gamma S binding assay using rat cerebellar membranes. The main goal of the study was to examine how the DMH end tail affects the activity properties of 2-AG (1) and its stable ether (2) and Urea analogues (5). The importance of the chain length was also explored by synthesizing 2-AG and 2-AGE derivatives (3 and 4) possessing the chain length C-21 instead of C-22. Replacement of the pentyl end chain with the DMH resulted in distinct potency decrease as compared to the reference compounds. The modification did not have Such a strong impact on the efficacy values. In fact, the efficacy of the derivatives of 2-AGE (2 and 4) was comparable or even improved. Introducing a more stable and hydrophilic urea bond led to a dramatic decrease in biological activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.12.007
• 作为产物：
  描述：

  花生四烯酸 在 吡啶 、 lead(IV) acetate 、 sodium tetrahydroborate 、 potassium hydrogensulfate 、 正丁基锂 、 高氯酸 、 双氧水 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 104.17h， 生成 16,16-dimethyl-docosa-5,8,11,14-all-cis-tetraenoic acid methyl ester
  参考文献：
  名称：

  Synthesis and Pharmacological Comparison of Dimethylheptyl and Pentyl Analogs of Anandamide

  摘要：

  (CH₂CH₃)₁₆-取代壬二烯酰胺醇胺（17a）及其酰胺类衍生物通过Wittig偶联反应合成，该偶联反应基于拉动奇族状酸丁酰胺的丁酰胺酸基团。这些酰胺类衍生物与内源性 cannabinoid 受体结合者 酯酸胆碱（anandamide，2a）及其酰胺类衍生物在药理学检测中对比分析，以考察其潜在的增强 Cannabinoid 模拟活性。在取代作用实验中，与相应的 anandamide（2a）及其酰胺类衍生物相比，DMH 类衍生物的受体亲和力显著提升（一个数量级），其与[H-3]CP55,940或[H-3]SR141716A相比，亲和力结果呈现出顺序差异。与 2a相比，在小鼠四联试验中进行的用于测试 Cannabinoid 活性时，17a的反应效力得以明显增强（数量级相仿或更高），在小鼠精巢中进行的用于测试 Cannabinoid 活性时，17a的反应效力并未出现任何明显增强。实验数据表明，经典植物类 cannabinoids 与 2a在构效关系上具有等价性，并说明多受体各或结合模式上的特性。

  DOI：

  10.1021/jm9702950

文献信息

• Novel eicosanoid analgesics
  申请人：——

  公开号：US20040122089A1

  公开（公告）日：2004-06-24

  Analogs of andandamide and arvanil have been found to act preferential at CB 1 and AR 1 receptors, and at receptors other than CB 1 and AR 1 . The analogs provide analgesic effects in vivo, and are useful in pain management. In addition, the analogs may be used as anti-proliferative/anti-tumor agents, vasodilators, and in other applications. Several of the anandamide and arvanil analogs are more potent than anandamide and arvanil.

  已发现与anandamide和arvanil类似物作用于CB1和AR1受体时具有优先性，并且还作用于非CB1和AR1受体。这些类似物在体内提供镇痛效果，并在疼痛管理中有用。此外，这些类似物还可以用作抗增殖/抗肿瘤剂、血管扩张剂以及其他应用。几种anandamide和arvanil类似物比anandamide和arvanil更有效。
• Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain
  作者：William J. Ryan、W. Kenneth Banner、Jenny L. Wiley、Billy R. Martin、Raj K. Razdan

  DOI：10.1021/jm970212f

  日期：1997.10.1

  To examine the effect of changing the length and branching of the end pentyl chain (C5H11) of anandamide (AN), various analogs 1a-h and 2a-f were synthesized from either the known aldehyde ester 6a or from the alcohol 6b and tested for their pharmacological activity. A reproducible procedure was developed for the conversion of arachidonic acid to 6a or 6b in gram quantities (overall yield 15%). The appropriate tetraene esters 7 were prepared by carrying out a Wittig reaction, between 6a and the ylide generated from the phosphonium salt of the appropriate alkyl halide or between the ylide of 6d (prepared from 6a --> 6b --> 6c --> 6d) and the appropriate alkyl aldehydes. They were then hydrolyzed to the corresponding acids and transformed into AN analogs 1 via their acid chlorides then treated with excess ethanolamine. alpha-Alkylation of esters 7 gave compounds 8 which were hydrolyzed to the corresponding acids. These acids via their acid chlorides and subsequent treatment with excess fluoroethylamine gave the target compounds 2. In this way analogs 1e and 2a-c were synthesized from 6d while all the remaining analogs were prepared from 6a. In order to assess the optimal length of the alkyl terminus, analogs 1a-d were prepared and showed moderately high affinities (18-55 nM). However analogs 1a-c failed to produce significant pharmacological effects at doses up to 30 mg/kg. Analog 1d was found to be a weak partial agonist. The reason for the lack of activity in 1a-c is presently not clear. Like the THCs, the branching of the end pentyl chain in AN (1e-h) increased potency both in in vitro and in vivo activities; the dimethylheptyl (DMH) analog 1e was the most potent in the series. Similar alkyl substitutions were carried out in the fluoro-2-methylanandamide series (2a-f), and all of these analogs had high receptor affinities (1-14 nM), the DMH analog 2a being the most potent. With a few exceptions they showed robust pharmacological effects, and AN-like profiles, It was shown that the SAR of the end pentyl chain in AN is very similar to that of THCs. However, the magnitude of enhanced potency observed when the side chain of THC was changed from straight to branched was not observed when the end chain of AN was similarly changed.
• The Synthesis of N-Vanillyl-arachidonoyl-amide (Arvanil) and its Analogs: An Improved Procedure for the Synthesis of the Key Synthon Methyl 14-Hydroxy-(all-cis)-5,8,11-tetradecatrienoate
  作者：Olivier Dasse、Anu Mahadevan、Luning Han、Billy R. Martin、Vincenzo Di Marzo、Raj K. Razdan

  DOI：10.1016/s0040-4020(00)00877-2

  日期：2000.11

  Several arvanil analogs were synthesized where the end n-pentyl chain was branched and carried substituents at the terminal end of the chain. A high yielding total synthesis of these analogs was developed from methyl hex-5-ynoate, which was converted to the synthon 6 in a facile five strip sequence (overall yield, 33%). The pharmacological profile of these novel analogs suggests that they may be acting through a novel site of action for anandamide (arachidonylethanolamide, AEA). (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and Pharmacological Comparison of Dimethylheptyl and Pentyl Analogs of Anandamide
  作者：Herbert H. Seltzman、Denise N. Fleming、Brian F. Thomas、Anne F. Gilliam、Deirdre S. McCallion、Roger G. Pertwee、David R. Compton、Billy R. Martin

  DOI：10.1021/jm9702950

  日期：1997.10.1

  (Dimethylheptyl)anandamide [(16,16-cimethyldocosa-cis-5,8,11,14-tetraenoyl)ethanolamine] (17a) and its amide analogs were synthesized by Wittig coupling of a ylide derived from a fragment of arachidonic acid. These amides were compared to the endogenous cannabinoid receptor ligand arachidonylethanolamide (anandamide, 2a) and its amide analogs in pharmacological assays for potential enhancement of cannabimimetic activities. The receptor affinity to rat brain membranes of the dimethylheptyl (DMH) analogs increased by an order of magnitude in most comparisons to the corresponding anandamides in displacement assays versus the cannabinoid agonist [H-3]CP 55,940 or antagonist [H-3]SR141716A, for which rank order differences in affinity were observed. An order of magnitude enhancement of potency with comparable or higher efficacy in behavioral assays in the mouse tetrad of tests of cannabinoid activity was observed in 17a versus 2a. In contrast, no enhancement in potency for the pentyl to DMH side chain exchange was seen in the mouse vas deferens assay. The data indicate a structural equivalence between classical plant cannabinoids and 2a as well as different receptor-ligand interactions that characterize multiple receptor sites or binding modes.

  (CH₂CH₃)₁₆-取代壬二烯酰胺醇胺（17a）及其酰胺类衍生物通过Wittig偶联反应合成，该偶联反应基于拉动奇族状酸丁酰胺的丁酰胺酸基团。这些酰胺类衍生物与内源性 cannabinoid 受体结合者 酯酸胆碱（anandamide，2a）及其酰胺类衍生物在药理学检测中对比分析，以考察其潜在的增强 Cannabinoid 模拟活性。在取代作用实验中，与相应的 anandamide（2a）及其酰胺类衍生物相比，DMH 类衍生物的受体亲和力显著提升（一个数量级），其与[H-3]CP55,940或[H-3]SR141716A相比，亲和力结果呈现出顺序差异。与 2a相比，在小鼠四联试验中进行的用于测试 Cannabinoid 活性时，17a的反应效力得以明显增强（数量级相仿或更高），在小鼠精巢中进行的用于测试 Cannabinoid 活性时，17a的反应效力并未出现任何明显增强。实验数据表明，经典植物类 cannabinoids 与 2a在构效关系上具有等价性，并说明多受体各或结合模式上的特性。
• Synthesis and CB1 receptor activities of dimethylheptyl derivatives of 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE)
  作者：Teija Parkkari、Outi M.H. Salo、Kristiina M. Huttunen、Juha R. Savinainen、Jarmo T. Laitinen、Antti Poso、Tapio Nevalainen、Tomi Järvinen

  DOI：10.1016/j.bmc.2005.12.007

  日期：2006.4

  Results from a factor analysis and activity studies of commercially available endocannabinoid-type compounds set the starting point for the current study where dimethylheptyl (DMH) analogues of two endocannabinoids, 2-arachidonoyl glycerol (2-AG) and 2-arachidonyl glyceryl ether (2-AGE), were synthesized and their ability to activate the CB1 receptors was determined by the [S-35]GTP gamma S binding assay using rat cerebellar membranes. The main goal of the study was to examine how the DMH end tail affects the activity properties of 2-AG (1) and its stable ether (2) and Urea analogues (5). The importance of the chain length was also explored by synthesizing 2-AG and 2-AGE derivatives (3 and 4) possessing the chain length C-21 instead of C-22. Replacement of the pentyl end chain with the DMH resulted in distinct potency decrease as compared to the reference compounds. The modification did not have Such a strong impact on the efficacy values. In fact, the efficacy of the derivatives of 2-AGE (2 and 4) was comparable or even improved. Introducing a more stable and hydrophilic urea bond led to a dramatic decrease in biological activity. (c) 2005 Elsevier Ltd. All rights reserved.