(6aR-trans)-3-(1-oxoheptyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-ol | 179044-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (6aR-trans)-3-(1-oxoheptyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-ol
• 英文别名: AMG 5；1-((6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-3-yl)heptan-1-one；1-[(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-3-yl]heptan-1-one
• CAS: 179044-95-2
• 化学式: C₂₃H₃₂O₃
• 分子量: 356.505
• InChiKey: QJSPAMOJYVCLHT-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6aR-trans)-3-(1-oxoheptyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-ol 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以93%的产率得到(-)-(1-hydroxy-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-3-yl)-α-(1'-hexyl)methanol
  参考文献：
  名称：

  Pharmacophoric Requirements for Cannabinoid Side Chains:  Multiple Bond and C1‘-Substituted Δ⁸-Tetrahydrocannabinols

  摘要：

  Accumulated evidence indicates that within the cannabinoid structure the aliphatic side chain plays a pivotal role in determining cannabimimetic activity. We describe the synthesis and affinities for the CB1 and CB2 receptors of a series of novel Delta(8)-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule. No analogue has the side-chain pharmacophore in a fully restricted conformation. However, our design serves to narrow down the scope of options for conformational requirements at the receptor active sites. All the analogues tested showed nanomolar or subnanomolar affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl)- 2-hexyl-1,3-dithiolane was found to possess very high affinity for both cannabinoid receptors(CB1, K-i = 0.32 nM; CB2, K-i = 0.52 nM).

  DOI：

  10.1021/jm970277i
• 作为产物：
  描述：

  1-(3,5-二甲氧基苯基)庚烷-1-酮 在 三氟化硼乙醚 、 三溴化硼 、 对甲苯磺酸 、 silver nitrate 作用下， 以 乙醇 、 二氯甲烷 、 苯 为溶剂， 反应 22.5h， 生成 (6aR-trans)-3-(1-oxoheptyl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-ol
  参考文献：
  名称：

  Pharmacophoric Requirements for Cannabinoid Side Chains:  Multiple Bond and C1‘-Substituted Δ⁸-Tetrahydrocannabinols

  摘要：

  Accumulated evidence indicates that within the cannabinoid structure the aliphatic side chain plays a pivotal role in determining cannabimimetic activity. We describe the synthesis and affinities for the CB1 and CB2 receptors of a series of novel Delta(8)-THC analogues in which the side-chain pharmacophores are conformationally more defined than in the parent molecule. No analogue has the side-chain pharmacophore in a fully restricted conformation. However, our design serves to narrow down the scope of options for conformational requirements at the receptor active sites. All the analogues tested showed nanomolar or subnanomolar affinities for the receptors; 2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl)- 2-hexyl-1,3-dithiolane was found to possess very high affinity for both cannabinoid receptors(CB1, K-i = 0.32 nM; CB2, K-i = 0.52 nM).

  DOI：

  10.1021/jm970277i

文献信息

• Pharmacophoric Requirements for the Cannabinoid Side Chain. Probing the Cannabinoid Receptor Subsite at C1‘
  作者：Demetris P. Papahatjis、Spyros P. Nikas、Therapia Kourouli、Ravi Chari、Wei Xu、Roger G. Pertwee、Alexandros Makriyannis

  DOI：10.1021/jm020558c

  日期：2003.7.1

  laboratories has provided evidence for the existence of a subsite within the CB1 and CB2 cannabinoid receptor binding domain corresponding to substituents at the benzylic side chain position of classical cannabinoids. The existence and stereochemical features of this subsite have now been probed through the synthesis of a novel series of (-)-Delta(8)-tetrahydrocannabinol analogues bearing C1'-ring substituents

  我们实验室的早期工作为CB1和CB2大麻素受体结合域内存在一个亚位点提供了证据，该位点对应于经典大麻素苄基侧链位置的取代基。现在已经通过合成一系列带有C1'-环取代基的（-）-Delta（8）-四氢大麻酚类似物来探索该亚位点的存在和立体化学特征。在本文所述的化合物中，具有C1'-二硫杂环戊烷（1c），C1'-二氧戊环（2d）和环戊基（2a）取代基的化合物表现出对CB1和CB2的最高亲和力。我们使用分子建模方法更好地定义了假定亚位点的立体化学极限。体外药理测试发现1c是有效的CB1激动剂。
• [EN] NOVEL CANNABINERGIC COMPOUNDS AND USES THEREOF<br/>[FR] NOUVEAUX COMPOSÉS CANNABINERGIQUES ET LEURS UTILISATIONS
  申请人：UNIV NORTHEASTERN

  公开号：WO2014039042A1

  公开（公告）日：2014-03-13

  Disclosed are compounds and compositions that modulate cannabinoid receptors, methods of modulating cannabinoid receptors, and methods of treating various disorders related to the modulation of cannabinoid receptors. This disclosure is directed to methods of treating cannabinoid dependence, neuropathy, inflammation, glaucoma, a neurodegenerative disorder, a motor function disorder, a gastrointestinal disorder, hypothermia, emesis, loss of appetite, or anorexia associated with AIDS.

  本发明涉及调节大麻素受体的化合物和组合物、调节大麻素受体的方法以及治疗与调节大麻素受体有关的各种疾病的方法。本公开涉及治疗大麻素依赖、神经病变、炎症、青光眼、神经退行性疾病、运动功能障碍、胃肠道疾病、低温、呕吐、食欲不振或艾滋病相关的厌食症的方法。
• Novel Cannabinergic Compounds and Uses Thereof
  申请人：Northeastern University

  公开号：US20160108016A1

  公开（公告）日：2016-04-21

  Disclosed are compounds and compositions that modulate cannabinoid receptors, methods of modulating cannabinoid receptors, and methods of treating various disorders related to the modulation of cannabinoid receptors. This disclosure is directed to methods of treating cannabinoid dependence, neuropathy, inflammation, glaucoma, a neurodegenerative disorder, a motor function disorder, a gastrointestinal disorder, hypothermia, emesis, loss of appetite, or anorexia associated with AIDS.

  本发明涉及调节大麻素受体的化合物和组合物、调节大麻素受体的方法以及治疗与调节大麻素受体相关的各种疾病的方法。本公开涉及治疗大麻素依赖、神经病变、炎症、青光眼、神经退行性疾病、运动功能障碍、肠道功能障碍、低体温、呕吐、食欲丧失或艾滋病相关的厌食症的方法。
• Cannabinergic compounds and uses thereof
  申请人：Northeastern University

  公开号：US10882838B2

  公开（公告）日：2021-01-05

  Disclosed are compounds and compositions that modulate cannabinoid receptors, methods of modulating cannabinoid receptors, and methods of treating various disorders related to the modulation of cannabinoid receptors. This disclosure is directed to methods of treating cannabinoid dependence, neuropathy, inflammation, glaucoma, a neurodegenerative disorder, a motor function disorder, a gastrointestinal disorder, hypothermia, emesis, loss of appetite, or anorexia associated with AIDS.

  公开了调节大麻素受体的化合物和组合物、调节大麻素受体的方法以及治疗与调节大麻素受体有关的各种疾病的方法。本公开涉及治疗与艾滋病相关的大麻素依赖、神经病变、炎症、青光眼、神经退行性疾病、运动功能障碍、胃肠道疾病、低体温、呕吐、食欲不振或厌食症的方法。
• Novel Cannabinergic Compounds And Uses Thereof
  申请人：Northeastern University

  公开号：US20190185443A1

  公开（公告）日：2019-06-20

  Disclosed are compounds and compositions that modulate cannabinoid receptors, methods of modulating cannabinoid receptors, and methods of treating various disorders related to the modulation of cannabinoid receptors. This disclosure is directed to methods of treating cannabinoid dependence, neuropathy, inflammation, glaucoma, a neurodegenerative disorder, a motor function disorder, a gastrointestinal disorder, hypothermia, emesis, loss of appetite, or anorexia associated with AIDS.