(4R,7aR,12bS)-7-methoxy-3,9-dimethyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline | 948313-72-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (4R,7aR,12bS)-7-methoxy-3,9-dimethyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline
• CAS: 948313-72-2
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: TXNGEXGIDNCWNK-CCKFTAQKSA-N

物化性质

• 沸点：
  440.2±45.0 °C(predicted)
• 密度：
  1.26±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R,7aR,12bS)-7-methoxy-3,9-dimethyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline 在 甲烷磺酸 作用下， 以45%的产率得到(R)-2-methoxy-6,10-dimethyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
  参考文献：
  名称：

  R-(−)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands

  摘要：

  Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10-methylaporphines were synthesized and their binding affinities at dopamine D, and D, receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain tissue were evaluated. Tested compounds displayed moderate to high affinity to 5-HT1A receptors but low affinity to D, and D-2 receptors. The most potent novel 5-HT1A agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.057
• 作为产物：
  描述：

  蒂巴因 在 bis-triphenylphosphine-palladium(II) chloride L-Selectride 、 三乙胺 、 三苯基膦 、 lithium chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4R,7aR,12bS)-7-methoxy-3,9-dimethyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline
  参考文献：
  名称：

  R-(−)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands

  摘要：

  Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10-methylaporphines were synthesized and their binding affinities at dopamine D, and D, receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain tissue were evaluated. Tested compounds displayed moderate to high affinity to 5-HT1A receptors but low affinity to D, and D-2 receptors. The most potent novel 5-HT1A agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.057

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF CHRONIC PAIN
  申请人：Cellixbio Private Limited

  公开号：US20150141451A1

  公开（公告）日：2015-05-21

  The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II, and methods for treating chronic pain in a disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of acute pain (such as post-operative pain), palliative care to alleviate the severe, chronic, disabling pain of terminal conditions such as cancer, and degenerative conditions such as rheumatoid arthritis, non-malignant chronic pain, chemotherapy induced pain, musculoskeletal pain, sciatica, radiculopathy pain, migraine, neuropathic pain, post herpetic neuralgia, neuralgia pain, multiple sclerosis, multiple sclerosis, restless legs syndrome (RLS), cluster headache, depression, fibromyalgia and amyotrophic lateral sclerosis (ALS).

  该发明涉及化合物I和化合物II或其药用可接受的盐，以及其多晶形、溶剂合物、对映体、立体异构体和水合物。包括化合物I或化合物II的有效量的药物组合物，以及用于治疗疾病中的慢性疼痛的方法，可以制备为口服、颊下、直肠、局部、经皮、经粘膜、静脉、肠外给药、糖浆或注射。这种组合物可以用于治疗急性疼痛（如术后疼痛），以缓解癌症等晚期疾病的严重、慢性、致残性疼痛，以及类风湿性关节炎、非恶性慢性疼痛、化疗引起的疼痛、肌肉骨骼疼痛、坐骨神经痛、神经根痛、偏头痛、神经性疼痛、带状疱疹后神经痛、神经痛、多发性硬化症、多发性硬化症、不安腿综合征（RLS）、集群性头痛、抑郁症、纤维肌痛和肌萎缩侧索硬化（ALS）的治疗。
• [EN] PROCESS FOR PREPARING 7&bgr;-SUBSTITUTED 6α,14α -ETHENOMORPHINANS AND 7&bgr;-SUBSTITUTED 6α,14α-ETHANOMORPHINANS<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ÉTHÉNO-6&Agr;,14&Agr;-MORPHINANES À SUBSTITUTION 7&Bgr; ET D'ÉTHANO-6&Agr;,14&Agr;-MORPHINANES À SUBSTITUTION 7&Bgr;
  申请人：RHODES TECHNOLOGIES

  公开号：WO2014102591A1

  公开（公告）日：2014-07-03

  The application is directed to a process for increasing the proportion of 7β-epimer in an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan, and specifically of compounds of Formula (I), wherein G, R2-R4, and are defined as set forth in the specification. The application is also directed to a process for purifying the 7β-epimer from an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α, 14α-ethanomorphinan. The application is also directed to a process for preparing 7β-substituted compounds of Formula Vb wherein G and R2 -R5 are defined as set forth in the specification.

  该申请涉及一种用于增加7-取代6α,14α-乙烯基吗啡或7-取代6α,14α-乙烷基吗啡的7α/7β-异构体混合物中7β-异构体比例的方法，具体地，涉及到公式（I）中G、R2-R4的化合物的方法，其中G、R2-R4的定义如规范中所述。该申请还涉及从7-取代6α,14α-乙烯基吗啡或7-取代6α,14α-乙烷基吗啡的7α/7β-异构体混合物中纯化7β-异构体的方法。该申请还涉及制备公式Vb中G和R2-R5定义如规范中所述的7β-取代化合物的方法。
• METHOD OF MANUFACTURING BUPRENORPHINE AND ANALOGUES THEREOF FROM ORIPAVINE
  申请人：SIEGFRIED AG

  公开号：US20170319574A1

  公开（公告）日：2017-11-09

  The invention relates to an improved method of preparing buprenorphine, a salt thereof, analogues of buprenorphine and their salts. In particular, the invention relates to a method of preparing buprenorphine and related products and salts in economic and ecologic ways having increased yields.

  本发明涉及一种改进的制备布洛芬啡、其盐、布洛芬啡类似物及其盐的方法。特别地，本发明涉及一种在经济和生态方面具有增加产量的制备布洛芬啡及相关产品和盐的方法。
• PROCESS FOR PREPARING 7BETA-SUBSTITUTED 6ALPHA,14ALPHA-ETHENOMORPHINANS AND 7BETA-SUBSTITUTED 6ALPHA,14ALPHA-ETHANOMORPHINANS
  申请人：REISCH Helge Alfred

  公开号：US20160068538A1

  公开（公告）日：2016-03-10

  The application is directed to a process for increasing the proportion of 7β-epimer in an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan, and specifically of compounds of Formula (I), wherein G, R 2 -R 4 , and are defined as set forth in the specification. The application is also directed to a process for purifying the 7β-epimer from an 7α/7β-epimer mixture of a 7-substituted 6α,14α-ethenomorphinan or a 7-substituted 6α,14α-ethanomorphinan. The application is also directed to a process for preparing 7β-substituted compounds of Formula V b wherein G and R 2 -R 5 are defined as set forth in the specification.

  本申请涉及一种用于增加7-取代-6α,14α-乙烯吗啡烷或7-取代-6α,14α-乙烷吗啡烷的7α/7β-表异构体混合物中7β-表异构体比例的方法，具体地，涉及公式（I）中G，R2-R4的化合物。本申请还涉及一种从7-取代-6α,14α-乙烯吗啡烷或7-取代-6α,14α-乙烷吗啡烷的7α/7β-表异构体混合物中纯化7β-表异构体的方法。本申请还涉及一种制备公式Vb中G和R2-R5所定义的7β-取代化合物的方法。
• R(-)-2-METHOXY-11-HYDROXYAPORPHINE AND DERIVATIVES THEREOF
  申请人：Neumeyer John L.

  公开号：US20110034446A1

  公开（公告）日：2011-02-10

  The invention features derivatives of R(−)-2-methoxy-11-hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  这项发明涉及R（-）-2-甲氧基-11-羟基阿品啡衍生物及其用于治疗帕金森病、性功能障碍和抑郁症的方法。