(5Z,8Z,11Z,14Z)-20-azidoeicosa-5,8,11,14-tetraenoic acid cyclopropylamide | 867281-00-3

• 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)-20-azidoeicosa-5,8,11,14-tetraenoic acid cyclopropylamide
• 英文别名: (5Z,8Z,11Z,14Z)-20-azido-N-cyclopropylicosa-5,8,11,14-tetraenamide
• CAS: 867281-00-3
• 化学式: C₂₃H₃₆N₄O
• 分子量: 384.565
• InChiKey: APVKIRJJFMYWIO-DTLRTWKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  28
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5Z,8Z,11Z,14Z)-20-azidoeicosa-5,8,11,14-tetraenoic acid cyclopropylamide 、 二硫化碳 在 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以85%的产率得到(5Z,8Z,11Z,14Z)-20-isothiocyanatoeicosa-5,8,11,14-tetraenoic acid cyclopropylamide
  参考文献：
  名称：

  High Affinity Electrophilic and Photoactivatable Covalent Endocannabinoid Probes for the CB1 Receptor

  摘要：

  We have designed and synthesized the first two high affinity covalent anandamide probes for the CB1 receptor by introducing either an electrophilic isothiocyanato or a photoactivatable azido group at the terminal carbon of the arachidonic acid moiety. The headgroup of these anandamide analogues was optimized by using a cyclopropylamide substituent to impart optimal CB1 affinity. Both 20-isothiocyanato-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (1, AM3677) and 20-azido-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (2, AM3661) exhibited high selectivities for the CB 1 receptor with K-i values of 1.3 and 0.9 nM, respectively. Using suitable experimental conditions, both ligands were shown to covalently label the CB1 receptor with high efficiency. These two covalent probes for the endocannabinoid CB1 binding site open the door for exploring the ligand binding motifs involved in the activation of the CB1 receptor by its endogenous ligand, anandamide.

  DOI：

  10.1021/jm050272i
• 作为产物：
  描述：

  methyl 20-hydroxyicosa-5,8,11,14-tetraynoate 在 喹啉 、 lithium hydroxide 、 Lindlar's catalyst 、 草酰氯 、 Zn(N3)2-2 pyr 、 偶氮二甲酸二异丙酯 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 49.5h， 生成 (5Z,8Z,11Z,14Z)-20-azidoeicosa-5,8,11,14-tetraenoic acid cyclopropylamide
  参考文献：
  名称：

  High Affinity Electrophilic and Photoactivatable Covalent Endocannabinoid Probes for the CB1 Receptor

  摘要：

  We have designed and synthesized the first two high affinity covalent anandamide probes for the CB1 receptor by introducing either an electrophilic isothiocyanato or a photoactivatable azido group at the terminal carbon of the arachidonic acid moiety. The headgroup of these anandamide analogues was optimized by using a cyclopropylamide substituent to impart optimal CB1 affinity. Both 20-isothiocyanato-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (1, AM3677) and 20-azido-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (2, AM3661) exhibited high selectivities for the CB 1 receptor with K-i values of 1.3 and 0.9 nM, respectively. Using suitable experimental conditions, both ligands were shown to covalently label the CB1 receptor with high efficiency. These two covalent probes for the endocannabinoid CB1 binding site open the door for exploring the ligand binding motifs involved in the activation of the CB1 receptor by its endogenous ligand, anandamide.

  DOI：

  10.1021/jm050272i

文献信息

• WO2006/44381
  申请人：——

  公开号：——

  公开（公告）日：——
• Cannabinergic Lipid Ligands
  申请人：Makriyannis Alexandros

  公开号：US20090163557A1

  公开（公告）日：2009-06-25

  One aspect of this disclosure relates generally to lipid compounds that exert diverse effects in the endocannabinoid system, such as regulating CB1 and CB2 receptor or moderating other bio-macromolecules within the endocannabinoid system. Some of the compounds showed improved receptor binding affinity, and/or improved receptor subtype selectivity, and improved bio-stability. Some of the compounds exhibit activities to regulate the enzymes that moderate the bio-disposal of endogenous cannabinoids, such as the fatty acid amide hydrolase (FAAH). Some of the compounds exhibit activities to inhibit the anandamide transporter. Other aspects of the invention are pharmaceutical preparations employing these ligands and methods of administering therapeutically effective amounts of the preparations to provide a physiological effect.
• US8202893B2
  申请人：——

  公开号：US8202893B2

  公开（公告）日：2012-06-19
• High Affinity Electrophilic and Photoactivatable Covalent Endocannabinoid Probes for the CB1 Receptor
  作者：Chen Li、Wei Xu、Subramanian K. Vadivel、Pusheng Fan、Alexandros Makriyannis

  DOI：10.1021/jm050272i

  日期：2005.10.1

  We have designed and synthesized the first two high affinity covalent anandamide probes for the CB1 receptor by introducing either an electrophilic isothiocyanato or a photoactivatable azido group at the terminal carbon of the arachidonic acid moiety. The headgroup of these anandamide analogues was optimized by using a cyclopropylamide substituent to impart optimal CB1 affinity. Both 20-isothiocyanato-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (1, AM3677) and 20-azido-eicosa-5,8,11,14-tetraenoic acid cyclopropylamide (2, AM3661) exhibited high selectivities for the CB 1 receptor with K-i values of 1.3 and 0.9 nM, respectively. Using suitable experimental conditions, both ligands were shown to covalently label the CB1 receptor with high efficiency. These two covalent probes for the endocannabinoid CB1 binding site open the door for exploring the ligand binding motifs involved in the activation of the CB1 receptor by its endogenous ligand, anandamide.