(4R)-4-[4-(2-methyloctan-2-yl)-2,6-dihydroxy-phenyl]-6,6-dimethyl-2-norpinanone | 182509-23-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R)-4-[4-(2-methyloctan-2-yl)-2,6-dihydroxy-phenyl]-6,6-dimethyl-2-norpinanone
• 英文别名: (1R,4R,5R)-4-(2,6-dihydroxy-4-(2-methyloctan-2-yl)phenyl)-6,6-dimethylbicyclo[3.1.1]heptan-2-one；(1R,4R,5R)-4-[2,6-dihydroxy-4-(2-methyloctan-2-yl)phenyl]-6,6-dimethylbicyclo[3.1.1]heptan-2-one
• CAS: 182509-23-5
• 化学式: C₂₄H₃₆O₃
• 分子量: 372.548
• InChiKey: FNTPCMPJXYNWGS-KURKYZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-4-[4-(2-methyloctan-2-yl)-2,6-dihydroxy-phenyl]-6,6-dimethyl-2-norpinanone 在 吡啶 、 三氟甲磺酸三甲基硅酯 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 (6aR,10aR)-6,6-dimethyl-3-(2-methyloctan-2-yl)-9-oxo-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-1-yl acetate
  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：

  (-)-nopinone enol acetate 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 生成 (4R)-4-[4-(2-methyloctan-2-yl)-2,6-dihydroxy-phenyl]-6,6-dimethyl-2-norpinanone
  参考文献：
  名称：

  大麻素。3. 9-酮大麻素的合成方法。总合成萘比隆。

  摘要：

  DOI：

  10.1021/jo00433a020

文献信息

• Novel Labelled Cannabinergic Ligands and Related Analogs
  申请人：Makriyannis Alexandros

  公开号：US20210300937A1

  公开（公告）日：2021-09-30

  Novel cannabinoid ligands represented by the general formulas I, II, and III and methods for preparation and use within which one or more of a fluorescent ligand, nitroxide spin label, metal chelate, biotin moiety, or group with enhanced polarity may be incorporated. The compounds can bind to and modulate the cannabinoid CB1 and CB2 receptors and thereby considered specific ligands for these receptors. Some of the disclosed compounds that bind to cannabinoid CB1 and CB2 receptors can exhibit tight or irreversible binding characteristics for these receptors. Due to the presence of the imaging/diagnostic and/or therapeutic functional groups including fluorescent groups, nitroxide spin labels, metal chelates, biotin moieties, and groups with enhanced polarity, the disclosed compounds may be useful as imaging/diagnostic tools and/or therapeutic agents.

  新型大麻素配体由一般公式I、II和III表示，以及用于制备和使用的方法，其中可以包含一个或多个荧光配体、亚硝基自旋标记、金属螯合物、生物素基团或具有增强极性的基团。这些化合物可以结合并调节大麻素CB1和CB2受体，因此被认为是这些受体的特异性配体。一些公开的结合到大麻素CB1和CB2受体的化合物可能表现出对这些受体的紧密或不可逆结合特性。由于含有成像/诊断和/或治疗功能基团，包括荧光基团、亚硝基自旋标记、金属螯合物、生物素基团和具有增强极性的基团，公开的这些化合物可能作为成像/诊断工具和/或治疗剂而有用。
• Selectivity in aromatic fluorination. Introduction of fluorine probes into nabilone
  作者：Marcus A. Tius、Joel K. Kawakami、W. Adam G. Hill、Alexandros Makriyannis

  DOI：10.1039/cc9960002085

  日期：——

  Selective fluorination of the aromatic ring of nabilone leads to functional analogues with diminished affinity for the CB1 receptor, thereby confirming the hypothesis that the phenolic hydroxy group is engaged in a hydrogen bonding interaction with the receptor.

  对纳比龙的芳香环进行选择性氟化，可得到对 CB1 受体亲和力减弱的功能类似物，从而证实了酚羟基与受体发生氢键相互作用的假设。
• Classical/Nonclassical Hybrid Cannabinoids:  Southern Aliphatic Chain-Functionalized C-6β Methyl, Ethyl, and Propyl Analogues
  作者：David J. Drake、Rader S. Jensen、Jakob Busch-Petersen、Joel K. Kawakami、M. Concepcion Fernandez-Garcia、Pusheng Fan、Alexandros Makriyannis、Marcus A. Tius

  DOI：10.1021/jm960677q

  日期：1998.9.1

  The stereoelectronic requirements for interaction of the southern aliphatic hydroxyl of cannabimimetic pharmacophores with the CB1 and CB2 receptors are explored. The stereoselective syntheses of three series of classical/nonclassical hybrid cannabinoids are described. These compounds were designed to investigate the importance of the southern aliphatic hydroxyl (SAH) pharmacophore for cannabimimetic

  探索了大麻模拟药效团的南部脂肪族羟基与CB1和CB2受体相互作用的立体电子学要求。描述了三个系列的经典/非经典杂种大麻素的立体选择性合成。设计这些化合物的目的是研究南部脂肪族羟基（SAH）药效团对拟南芥活性的重要性。这些6beta-（羟烷基）二氢苯并吡喃类似物中SAH部分的链长从6beta-羟甲基到6beta-（ω-羟乙基）和6beta-（ω-羟丙基）的变化以及通过氢化物取代羟基官能团的作用和碘化物的报道。我们的结果表明，SAH药效团对大麻素活性的影响不如C-3脂族链明显。此外，似乎该南方分子组分能够与受体上的两个不同的亚位点相互作用，并且这种相互作用的性质由C-6β烷基上的末端取代基决定。其中一个亚位点可以容纳相对极性的SAH药效团，而第二个亚位点则与更多的疏水性C-6β取代基相互作用，并且可以容纳由三环大麻素模板中的三个亚甲基碳分隔的大型球形药效团。
• 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。