(6aR,10aR)-1-acetoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid | 137945-50-7

• 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,10aR)-1-acetoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid
• 英文别名: (6aR,10aR)-1-acetyloxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene-9-carboxylic acid
• CAS: 137945-50-7
• 化学式: C₂₇H₃₈O₅
• 分子量: 442.596
• InChiKey: NAPXWHRSAVXKIB-NHCUHLMSSA-N

物化性质

• 沸点：
  538.2±50.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (6aR,10aR)-1-acetoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid 在 水 、 sodium hydroxide 作用下， 以 甲基叔丁基醚 为溶剂， 反应 4.0h， 以90.7%的产率得到(6aR,10aR)-1-羟基-6,6-二甲基-3-(2-甲基辛-2-基)-6a,7,10,10a-四氢苯并[c]色原烯-9-羧酸
  参考文献：
  名称：

  [EN] ULTRAPURE TETRAHYDROCANNABINOL-11-OIC ACIDS
  [FR] ACIDES TÉTRAHYDROCANNABINOL-11-OÏQUES ULTRAPURS

  摘要：

  公开号：

  WO2014127016A3
• 作为产物：
  描述：

  11-oxo-(6aR,10aR)-3-(1',1'-dimethylheptyl)-Δ⁸-tetrahydrocannabinol 1-O-acetate 在 双氧水 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.0h， 生成 (6aR,10aR)-1-acetoxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene-9-carboxylic acid
  参考文献：
  名称：

  Ultrapure ajulemic acid has improved CB2 selectivity with reduced CB1 activity

  摘要：

  Ajulemic acid, a side-chain analog of Delta(8)-THC-11-oic acid, was designed as a potent therapeutic agent free of the psychotropic adverse effects typical of most cannabinoids. Subsequent studies of ajulemic acid have yielded widely divergent findings on the occurrence of these adverse effects. To help resolve these discrepancies, we have prepared highly purified ajulemic acid using a different synthetic method than previously reported in the literature and compared its cannabinoid receptor binding constants with those obtained using several other preparations from different sources. Whereas CB2 binding did not vary greatly among all of the samples, the CB1 binding showed a wide range of affinities. The highly purified product (JBT-101) reported here had the weakest affinity for CB1 while the original preparation (HU-239) showed the strongest affinity for CBI. The CB1/CB2 ratio of affinities was 12.3 for JBT-101 whereas that for HU-239 was 0.19, a 65-fold difference. Functional responses such as catalepsy and hypothermia using JBT-101 versus HU-239 displayed reduced CB1 activity in keeping with the receptor binding data. Thus, earlier conclusions on the limited therapeutic index for ajulemic acid need to be reconsidered in the light of the data now obtained using JBT-101. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.062

文献信息

• Synthetic nonpsychotropic cannabinoids with potent antiinflammatory, analgesic, and leukocyte antiadhesion activities
  作者：Sumner H. Burstein、Charlene A. Audette、Aviva Breuer、William A. Devane、Sharona Colodner、Sharon A. Doyle、Raphael Mechoulam

  DOI：10.1021/jm00095a007

  日期：1992.8

  contrast to the above tests where the 3R,4R compounds are more active than the 3S,4S enantiomers. Finally, in agreement with earlier reports on the naturally occurring pentyl side chain acids, the synthetic acids showed little activity in producing catalepsy in the mouse, suggesting that they would be nonpsychotropic in humans.

  设计治疗上有用的大麻素的两种策略已经结合在一起，以产生具有大大增强的抗炎活性并且具有较低的不良副作用可能性的化合物。已经合成了对映体大麻素，其在第7位具有一个羧酸基团，在第5'位具有一个伸长和分支的烷基侧链，并测试了其抗炎活性。当以10微克/千克的剂量口服给予时，它们可有效减少花生四烯酸或血小板活化因子诱导的小鼠爪水肿。在以与爪水肿试验相同的剂量范围内口服给予大麻素的小鼠的腹膜细胞中，白细胞对培养皿的粘附也降低了。在小鼠热板试验中可以观察到抗伤害作用。然而，与上述测试相反，几乎没有立体化学偏好，在上述测试中，3R，4R化合物比3S，4S对映体活性更高。最后，与早先有关天然戊基侧链酸的报道相一致，合成酸在小鼠中产生僵直的作用很小，这表明它们在人类中是非精神病的。
• Treatment of interstitial cystitis using (6aR,10aR)-delta8-tetrahydrocannabinol-11-OIC acids
  申请人：Sandage W. Bobby

  公开号：US20060128794A1

  公开（公告）日：2006-06-15

  The present invention relates to non-psychoactive derivatives of tetrahydrocannabinol, which are useful in treating interstitial cystitis and relieving symptoms thereof. The invention uses (6aR,10aR)-Δ 8 -tetrahydrocannabinol-11-oic acids (hereinafter referred to as (6aR,10aR)-Δ 8 -THC-11-oic acid), as well as pharmaceutical compositions containing the (6aR,10aR)-Δ 8 -THC-11-oic acids, for treatment of interstitial cystitis in a mammal. The invention further covers methods of formulating and administering the compounds and pharmaceutical compositions as therapeutic agents in the treatment of interstitial cystitis, with particularly preferred administration routes being oral and via intravesicular instillation.

  本发明涉及四氢大麻酚的非精神活性衍生物，其在治疗间质性膀胱炎和缓解其症状方面有用。本发明使用(6aR,10aR)-Δ8-四氢大麻酚-11-酸（以下简称(6aR,10aR)-Δ8-THC-11-酸），以及含有(6aR,10aR)-Δ8-THC-11-酸的制药组合物，用于哺乳动物间质性膀胱炎的治疗。本发明还涵盖了制定和管理化合物和制药组合物的方法，作为间质性膀胱炎治疗的治疗剂，特别是口服和经膀胱灌注的途径。
• ANTI-EMETIC USES OF (3R, 4R)-DELTA8-TETRAHYDROCANNABINOL-11-OIC ACIDS
  申请人：Sandage W. Bobby

  公开号：US20070099988A1

  公开（公告）日：2007-05-03

  The present invention relates to non-psychoactive derivatives of tetrahydrocannabinol, (3R,4R)-Δ 8 -THC-11-oic acids, for treating or preventing nausea and relieving symptoms thereof.

  本发明涉及非精神活性的四氢大麻酚衍生物，(3R,4R)-Δ8-THC-11-油酸，用于治疗或预防恶心并缓解其症状。
• [EN] CANNABINOIDS AND USES THEREOF<br/>[FR] CANNABINOÏDES ET UTILISATIONS ASSOCIÉES
  申请人：CORBUS PHARMACEUTICALS INC

  公开号：WO2021087127A8

  公开（公告）日：2021-07-15
• [EN] CANNABINOIDS AND USES THEREOF<br/>[FR] CANNABINOÏDES ET LEURS UTILISATIONS
  申请人：CORBUS PHARMACEUTICALS INC

  公开号：WO2021113656A9

  公开（公告）日：2022-04-21