5'-bromo-1',1'-dimethyl-Δ⁸-tetrahydrocannabinol | 152674-96-9

• 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: 5'-bromo-1',1'-dimethyl-Δ⁸-tetrahydrocannabinol
• 英文别名: B4C266Ftr4；(6aR,10aR)-3-(6-bromo-2-methylhexan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol
• CAS: 152674-96-9
• 化学式: C₂₃H₃₃BrO₂
• 分子量: 421.418
• InChiKey: RJPGJHLVEUSRRA-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5'-bromo-1',1'-dimethyl-Δ⁸-tetrahydrocannabinol 在 4-二甲氨基吡啶 、 氢氧化钾 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 51.0h， 生成 O 606
  参考文献：
  名称：

  Potent Cyano and Carboxamido Side-Chain Analogues of 1‘,1‘-Dimethyl-Δ⁸-Tetrahydrocannabinol

  摘要：

  The synthesis and pharmacological profile of several cyano (1a-e) and carboxamido (2a-h) side-chain-substituted analogues of 1',1'-dimethyl-Delta(8)-THC are described. Commercially available cyano compound 3 was transformed to the resorcinol 6 in a three-step sequence. Condensation of 6 with p-menth-2-ene-1,8-diol formed the THC 7a which, with sodium cyanide/ DMSO, gave Ib. Protection of the phenol in 7a as the MOM derivative provided the common intermediate 8 for the synthesis of 1a,c,e. Compound 1d was also synthesized from 7a via the aldehyde 9a. Base hydrolysis of 1b gave the acid 10 which, via its acid chloride and subsequent treatment with the appropriate amine, formed the target compounds 2a-h. The pharmacological profile indicated that the cyano analogues 1a-e had very high CB1 binding affinity (0.36-13 nM) and high in vivo potency as agonists. Two analogues (1a,b) had extremely high potency in the mouse tetrad tests. The dimethylcarboxamido analogue 2a showed a similar profile to 1a,b. The high potency was also retained in analogue 2c. In contrast the sulfonamide analogue 2d was unique as it had greater affinity than Delta(9)-THC, yet it was practically devoid of agonist effects. This study suggests that the incorporation of a cyano or an amide substituent in the side chain of Delta(8)-THC-DMH can enhance potency and can also lead to compounds with a unique profile which have high binding affinity and are practically devoid of agonist effects.

  DOI：

  10.1021/jm9803875
• 作为产物：
  描述：

  3,5-二甲氧基苯腈 在 盐酸 、 三溴化硼 、 四氯化钛 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 7.17h， 生成 5'-bromo-1',1'-dimethyl-Δ⁸-tetrahydrocannabinol
  参考文献：
  名称：

  Potent Cyano and Carboxamido Side-Chain Analogues of 1‘,1‘-Dimethyl-Δ⁸-Tetrahydrocannabinol

  摘要：

  The synthesis and pharmacological profile of several cyano (1a-e) and carboxamido (2a-h) side-chain-substituted analogues of 1',1'-dimethyl-Delta(8)-THC are described. Commercially available cyano compound 3 was transformed to the resorcinol 6 in a three-step sequence. Condensation of 6 with p-menth-2-ene-1,8-diol formed the THC 7a which, with sodium cyanide/ DMSO, gave Ib. Protection of the phenol in 7a as the MOM derivative provided the common intermediate 8 for the synthesis of 1a,c,e. Compound 1d was also synthesized from 7a via the aldehyde 9a. Base hydrolysis of 1b gave the acid 10 which, via its acid chloride and subsequent treatment with the appropriate amine, formed the target compounds 2a-h. The pharmacological profile indicated that the cyano analogues 1a-e had very high CB1 binding affinity (0.36-13 nM) and high in vivo potency as agonists. Two analogues (1a,b) had extremely high potency in the mouse tetrad tests. The dimethylcarboxamido analogue 2a showed a similar profile to 1a,b. The high potency was also retained in analogue 2c. In contrast the sulfonamide analogue 2d was unique as it had greater affinity than Delta(9)-THC, yet it was practically devoid of agonist effects. This study suggests that the incorporation of a cyano or an amide substituent in the side chain of Delta(8)-THC-DMH can enhance potency and can also lead to compounds with a unique profile which have high binding affinity and are practically devoid of agonist effects.

  DOI：

  10.1021/jm9803875

文献信息

• Sulfonamide cannabinoid agonists and antagonists
  申请人：Martin R. Billy

  公开号：US20050096379A1

  公开（公告）日：2005-05-05

  Cannabinoid agonists and antagonists are provided for use in the treatment of disorders such as acute and chronic pain, inflammation, loss of appetite, convulsions, multiple sclerosis, nausea and vomiting. The cannabinoid agonists and antagonists contain a sulfonamide moiety incorporated into the cannabinoid side chain, and the side chain itself may be saturated or unsaturated.

  大麻素激动剂和拮抗剂可用于治疗急性和慢性疼痛、炎症、食欲减退、抽搐、多发性硬化、恶心和呕吐等疾病。这些大麻素激动剂和拮抗剂包含一个磺胺基团并入大麻素侧链中，侧链本身可能是饱和或不饱和的。
• [EN] WATER-SOLUBLE CANNABINOIDS<br/>[FR] CANNABINOIDES SOLUBLES DANS L'EAU
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2006012176A1

  公开（公告）日：2006-02-02

  Water-soluble cannabinoid compounds that are agonists of CB1 and CB2 cannabinoid receptors are provided. The compounds are made water-soluble by derivatization of the alkyl side chain and/or the phenolic hydroxyl group of tetrahydrocannabinol. The water-soluble cannabinoids are useful for the treatment of appetite loss, pain, multiple sclerosis, nausea and vomiting, and epilepsy.

  提供了一种可以溶于水的作用于CB1和CB2大麻素受体的大麻素类化合物。通过对四氢大麻酚的烷基侧链和/或酚羟基进行衍生化，使这些化合物可以溶于水。这些水溶性大麻素化合物可用于治疗食欲不振、疼痛、多发性硬化症、恶心和呕吐以及癫痫等疾病。
• CANNABINERGIC NITRATE ESTERS AND RELATED ANALOGS
  申请人：Northeastern University

  公开号：US20160002195A1

  公开（公告）日：2016-01-07

  The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.

  本技术涉及新型大麻素硝酸酯及其类似物、制备方法、制药组合物及其作为药物、药理工具和/或生物标志物的使用方法。这些新型大麻素硝酸酯化合物提供了治疗各种疾病和医学障碍的有用药物。
• Cannabinergic nitrate esters and related analogs
  申请人：Northeastern University

  公开号：US10221164B2

  公开（公告）日：2019-03-05

  The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.

  本技术涉及新型大麻素能硝酸酯和相关类似物、制备工艺、药物组合物及其作为药物、药理学工具和/或生物标记物的使用方法。新型大麻素能硝酸酯化合物可提供治疗各种疾病和医学紊乱的药物。
• Cannabinergic Nitrate Esters And Related Analogs
  申请人：Northeastern University

  公开号：US20170210728A1

  公开（公告）日：2017-07-27

  The present technology relates to novel cannabinergic nitrate esters and related analogs, process of preparation, pharmaceutical compositions and their methods of use as medicaments, pharmacological tools and/or biomarkers. The novel cannabinergic nitrate ester compounds provide medicaments useful in treating a variety of diseases and medical disorders.