3-[(3R,4R)-5-hydroxy-4-(hydroxymethyl)-2,2-dimethyl-7-(2-methyloctan-2-yl)chroman-3-yl]propanoic acid | 1541205-35-9

• 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: 3-[(3R,4R)-5-hydroxy-4-(hydroxymethyl)-2,2-dimethyl-7-(2-methyloctan-2-yl)chroman-3-yl]propanoic acid
• 英文别名: 3-[(3R,4R)-5-hydroxy-4-(hydroxymethyl)-2,2-dimethyl-7-(2-methyloctan-2-yl)-3,4-dihydrochromen-3-yl]propanoic acid
• CAS: 1541205-35-9
• 化学式: C₂₄H₃₈O₅
• 分子量: 406.563
• InChiKey: HJMNQQXEECLHNG-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[(3R,4R)-5-hydroxy-4-(hydroxymethyl)-2,2-dimethyl-7-(2-methyloctan-2-yl)chroman-3-yl]propanoic acid 在 4-二甲氨基吡啶 、 甲烷磺酸 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以79%的产率得到(5aR,11bR)-11-hydroxy-6,6-dimethyl-9-(2-methyloctan-2-yl)-1,4,5,5a,6,11b-hexahydro-3H-oxepino[4,3-c]chromen-3-one
  参考文献：
  名称：

  C-Ring Cannabinoid Lactones: A Novel Cannabinergic Chemotype

  摘要：

  As a part of our controlled-deactivation ligand development project, we recently disclosed a series of (-)-Delta(8)-tetrahydrocannabinols (THCs) with a metabolically labile ester group at the 2'-position of the side chain. Now, we have replaced the C-ring in the classical THC structure with a hydrolyzable seven-membered lactone. One of the synthesized analogues binds with high affinity to the CB1 receptor (K-i; = 4.6 nM) and exhibitsmuch lower affinities for the mCB2 and the hCB2. Also, in vitro functional characterization found the compound to be an agonist at rCB1. Consistent with our rational design, the lead cannabinergic lactone identified here is susceptible to metabolic inactivation by plasma esterases, while the respective acid metabolite is inactive at CB receptors. These results are highlighted with molecular modeling of the two regiosomeric lactones.

  DOI：

  10.1021/ml4005304
• 作为产物：
  描述：

  nabilone 在 吡啶 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 3-[(3R,4R)-5-hydroxy-4-(hydroxymethyl)-2,2-dimethyl-7-(2-methyloctan-2-yl)chroman-3-yl]propanoic acid
  参考文献：
  名称：

  C-Ring Cannabinoid Lactones: A Novel Cannabinergic Chemotype

  摘要：

  As a part of our controlled-deactivation ligand development project, we recently disclosed a series of (-)-Delta(8)-tetrahydrocannabinols (THCs) with a metabolically labile ester group at the 2'-position of the side chain. Now, we have replaced the C-ring in the classical THC structure with a hydrolyzable seven-membered lactone. One of the synthesized analogues binds with high affinity to the CB1 receptor (K-i; = 4.6 nM) and exhibitsmuch lower affinities for the mCB2 and the hCB2. Also, in vitro functional characterization found the compound to be an agonist at rCB1. Consistent with our rational design, the lead cannabinergic lactone identified here is susceptible to metabolic inactivation by plasma esterases, while the respective acid metabolite is inactive at CB receptors. These results are highlighted with molecular modeling of the two regiosomeric lactones.

  DOI：

  10.1021/ml4005304

文献信息

• [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：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.
• Cannabinergic Compounds And Uses Thereof
  申请人：Northeastern University

  公开号：US20210101878A1

  公开（公告）日：2021-04-08

  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.
• C-Ring Cannabinoid Lactones: A Novel Cannabinergic Chemotype
  作者：Rishi Sharma、Spyros P. Nikas、Jason Jianxin Guo、Srikrishnan Mallipeddi、JodiAnne T. Wood、Alexandros Makriyannis

  DOI：10.1021/ml4005304

  日期：2014.4.10

  As a part of our controlled-deactivation ligand development project, we recently disclosed a series of (-)-Delta(8)-tetrahydrocannabinols (THCs) with a metabolically labile ester group at the 2'-position of the side chain. Now, we have replaced the C-ring in the classical THC structure with a hydrolyzable seven-membered lactone. One of the synthesized analogues binds with high affinity to the CB1 receptor (K-i; = 4.6 nM) and exhibitsmuch lower affinities for the mCB2 and the hCB2. Also, in vitro functional characterization found the compound to be an agonist at rCB1. Consistent with our rational design, the lead cannabinergic lactone identified here is susceptible to metabolic inactivation by plasma esterases, while the respective acid metabolite is inactive at CB receptors. These results are highlighted with molecular modeling of the two regiosomeric lactones.