(5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid | 17711-21-6

• 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: (5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid
• CAS: 17711-21-6
• 化学式: C₂₁H₃₄O₂
• 分子量: 318.5
• InChiKey: XUTVYIBVBKBHHN-ZKWNWVNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  23
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 2.17h， 生成 (5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid (2-hydroxy-ethyl)-amide
  参考文献：
  名称：

  Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain

  摘要：

  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.

  DOI：

  10.1021/jm970212f
• 作为产物：
  描述：

  花生四烯酸 在 吡啶 、 lead(IV) acetate 、 lithium hydroxide 、 正丁基锂 、 高氯酸 、 草酰氯 、 双氧水 、 sodium sulfate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 6.75h， 生成 (5Z,8Z,11Z,14Z)-Henicosa-5,8,11,14-tetraenoic acid
  参考文献：
  名称：

  Potent Anandamide Analogs:  The Effect of Changing the Length and Branching of the End Pentyl Chain

  摘要：

  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.

  DOI：

  10.1021/jm970212f

文献信息

• Optical Imaging Contrast Agents For Imaging Lung Cancer
  申请人：Klaveness Jo

  公开号：US20070212305A1

  公开（公告）日：2007-09-13

  The invention provides contrast agents for optical imaging of lung cancer in patients. The contrast agents may be used in diagnosis of lung cancer, for follow up of progress in disease development, for follow up of treatment of lung cancer and for surgical guidance. Further, the invention provides methods for optical imaging of lung cancer in patients.

  这项发明提供了用于患者肺癌光学成像的对比剂。这些对比剂可用于肺癌的诊断，用于随访疾病进展，用于随访肺癌治疗以及用于手术指导。此外，该发明还提供了用于患者肺癌光学成像的方法。
• Glycosylceramide analogues
  申请人：Jiang Zi-Hua

  公开号：US20060116331A1

  公开（公告）日：2006-06-01

  Glycosylceramide analogues are disclosed in which the ceramide moiety and optionally the carbohydrate moiety are modified or replaced. These analogues are useful as immunomodulators, antitumor agents, and as other pharmaceutical agents.

  公开了糖基甘油酰胺类似物，其中的神经酰胺分子和可选的碳水化合物分子被修饰或取代。这些类似物可用作免疫调节剂、抗肿瘤剂和其他药物。
• GLYCOSYLCERAMIDE ANALOGUES
  申请人：BIOMIRA, INC.

  公开号：EP1572114A2

  公开（公告）日：2005-09-14
• [EN] GLYCOSYLCERAMIDE ANALOGUES<br/>[FR] ANALOGUES DU GLYCOSYLCERAMIDE
  申请人：BIOMIRA INC

  公开号：WO2004028475A2

  公开（公告）日：2004-04-08

  Glycosylceramide analogues are disclosed in which the ceramide moiety and optionally the carbohydrate moiety are modified or replaced. These analogues are useful as immunomodulators, antitumor agents, and as other pharmaceutical agents.
• 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.