(R)-二甲基(1-甲基-4-氧代-3,3-二苯基己基)氯化铵 | 5967-73-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (R)-二甲基(1-甲基-4-氧代-3,3-二苯基己基)氯化铵
• 英文名称: (R)-methadone hydrochloride
• 英文别名: (R)-6-(dimethylamino)-4,4-diphenyl-3-heptanone hydrochloride；levomethadone hydrochloride；(-)-Methadone hydrochloride；(6R)-6-(dimethylamino)-4,4-diphenylheptan-3-one;hydron;chloride
• CAS: 5967-73-7
• 化学式: C₂₁H₂₇NO*ClH
• 分子量: 345.912
• InChiKey: FJQXCDYVZAHXNS-UNTBIKODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.71
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  20.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-二甲基(1-甲基-4-氧代-3,3-二苯基己基)氯化铵 在 ammonium hydroxide 作用下， 以 水 为溶剂， 以99%的产率得到美沙酮
  参考文献：
  名称：

  [EN] "A NOVEL PROCESS FOR CHIRAL RESOLUTION OF HIGHLY PURE (6R)-6-(DIMETHYLAMINO)-4,4-DIPHENYL-3-HEPTANONE FROM RACEMIC METHADONE HYDROCHLORIDE"
  [FR] NOUVEAU PROCÉDÉ DE RÉSOLUTION CHIRALE DE (6R)-6-(DIMÉTHYLAMINO)-4,4-DIPHÉNYL-3-HEPTANONE DE HAUTE PURETÉ À PARTIR DE CHLORHYDRATE DE MÉTHADONE RACÉMIQUE

  摘要：

  本发明公开了一种改进的制备纯（二甲基氨基）-4,4-二苯基-3-庚酮及其盐酸盐的方法。

  公开号：

  WO2016103274A1
• 作为产物：
  描述：

  左美沙酮 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以93%的产率得到(R)-二甲基(1-甲基-4-氧代-3,3-二苯基己基)氯化铵
  参考文献：
  名称：

  [EN] "A NOVEL PROCESS FOR CHIRAL RESOLUTION OF HIGHLY PURE (6R)-6-(DIMETHYLAMINO)-4,4-DIPHENYL-3-HEPTANONE FROM RACEMIC METHADONE HYDROCHLORIDE"
  [FR] NOUVEAU PROCÉDÉ DE RÉSOLUTION CHIRALE DE (6R)-6-(DIMÉTHYLAMINO)-4,4-DIPHÉNYL-3-HEPTANONE DE HAUTE PURETÉ À PARTIR DE CHLORHYDRATE DE MÉTHADONE RACÉMIQUE

  摘要：

  本发明公开了一种改进的制备纯（二甲基氨基）-4,4-二苯基-3-庚酮及其盐酸盐的方法。

  公开号：

  WO2016103274A1

文献信息

• METHODS AND SYSTEMS FOR DESIGNING AND/OR CHARACTERIZING SOLUBLE LIPIDATED LIGAND AGENTS
  申请人：TUFTS MEDICAL CENTER

  公开号：US20160052982A1

  公开（公告）日：2016-02-25

  The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

  本申请提供了制备可溶性脂质化配体药剂的方法，包括配体实体和脂质实体，并在某些实施例中提供了这些组分的相关参数，从而使得能够适当选择组分来组装出针对任何感兴趣的靶点的活性药剂。
• Non-Racemic Mixtures of Various Ratios of D- and L-methadone and Methods of Treating Pain Using the Same
  申请人：MIRONER Y. Eugene

  公开号：US20160235691A1

  公开（公告）日：2016-08-18

  Non-racemic mixtures of D- and L-methadone containing a ratio ranging from about 2.5:1 to about 3.5:1 by weight of D-methadone to L-methadone, such as for example about 2.9:1 to about 3.1:1 by weight of D-methadone to L-methadone, or about 3:1 by weight of D-methadone to L-methadone, have been found to exhibit surprising and unexpected beneficial results in the treatment of neuropathic pain. Additionally, non-racemic mixtures of D- and L-methadone containing a ratio ranging from about 2.5:1 to about 3.5:1 by weight of D-methadone to L-methadone, about 2.9:1 to about 3.1:1 by weight of D-methadone to L-methadone, or for example about 3:1 by weight of D-methadone to L-methadone, in combination with other non-methadone opioids have been found to exhibit surprising and unexpected beneficial results in the treatment of mixed pain.

  非外消旋混合物的D-和L-美沙酮，其含有D-美沙酮与L-美沙酮按重量比大约为2.5:1至大约3.5:1，例如大约为2.9:1至大约3.1:1，或者大约为3:1，已被发现在神经痛的治疗中表现出令人惊讶和意想不到的益处。此外，非外消旋混合物的D-和L-美沙酮，其含有D-美沙酮与L-美沙酮按重量比大约为2.5:1至大约3.5:1，大约为2.9:1至大约3.1:1，或者例如大约为3:1，与其他非美沙酮类阿片类药物结合使用，已被发现在混合性疼痛的治疗中表现出令人惊讶和意想不到的益处。
• [EN] SYNTHESIS OF LEVOMETHADONE HYDROCHLORIDE OR DEXTROMETHADONE HYDROCHLORIDE AND METHODS FOR USE THEREOF<br/>[FR] SYNTHÈSE DE CHLORHYDRATE DE LÉVOMÉTHADONE OU DE CHLORHYDRATE DE DEXTROMÉTHADONE ET LEURS MÉTHODES D'UTILISATION
  申请人：CODY LABORATORIES INC

  公开号：WO2017035224A1

  公开（公告）日：2017-03-02

  Highly efficient methods for synthesis of levomethadone hydrochloride or dextromethadone hydrochloride are provided starting from D-alanine, or L-alanine, respectively, with retention of configuration. Methods for treating a subject are provided comprising administering a composition comprising an effective amount of levomethadone hydrochloride having not more than 10 ppm dextromethadone.

  提供了高效的合成左美沙酮盐酸盐或右美沙酮盐酸盐的方法，从D-丙氨酸或L-丙氨酸开始，保持构型不变。提供了治疗对象的方法，包括给予含有不超过10ppm右美沙酮的左美沙酮盐酸盐有效量的组合物。
• Methadone chiral isolate as an improved pharmaceutical
  申请人：Somberg John Charin

  公开号：US20100010096A1

  公开（公告）日：2010-01-14

  Methadone is a frequently employed agent for the treatment of drug addiction and the treatment of pain. Methadone prolongs the cardiac action potential, which on the surface electrocardiogram is represented by QT prolongation. This QT prolongation is known to increase the risk for the development of cardiac arrhythmias, especially the form of ventricular tachycardia known as Torsade de Pointes. For this reason, the FDA has inserted a “black box” warning for potential life threatening arrhythmias. The invention described in this application is the surprising finding that the R-isomer of methadone causes less inhibition of the potassium channel, IKr and thus would have less of a chance of causing life threatening arrhythmias. What is claimed is a method of chirally separating methadone with one isomer having less QT prolongation and more analgesic action that would make a superior pharmacologic agent than the racemate R,S methadone.

  美沙酮是一种常用药物，用于治疗药物成瘾和疼痛。美沙酮延长心脏动作电位，在表面心电图上表现为QT间期延长。已知这种QT间期延长会增加心律失常的风险，特别是一种称为扭转型室速的心室心律失常。因此，美国食品药品监督管理局（FDA）已经对潜在的危及生命的心律失常发布了“黑盒子”警告。本申请所描述的发明是发现美沙酮的R-异构体对钾通道IKr的抑制作用较小，因此较少引起危及生命的心律失常的意外发现。所要求的是一种手性分离美沙酮的方法，其中一种异构体具有较少的QT间期延长和更多的镇痛作用，使其成为比混合物R,S-美沙酮更优越的药理剂。
• SYNTHESIS OF LEVOMETHADONE HYDROCHLORIDE
  申请人：Safaei-Ghomi Javad

  公开号：US20200277250A1

  公开（公告）日：2020-09-03

  A method for synthesizing levomethadone hydrochloride including producing (R)-2-(dimethylamino)propan-1-ol by reducing N,N-dimethyl-D-alanine using borax, forming (R)-1-chloro-N,N-dimethylpropane-2-amine hydrochloride by chlorinating the (R)-2-(dimethylamino)propan-1-ol, synthesizing levomethadone nitrile hydrochloride by mixing the (R)-1-chloro-N,N-dimethylpropane-2-amine and diphenylacetonitrile with potassium t-butoxide and producing levomethadone hydrochloride by exposing the levomethadone nitrile hydrochloride to a Grignard reagent.

  一种合成左旋美沙酮盐酸盐的方法，包括通过使用硼砂还原N,N-二甲基-D-丙氨酸生成(R)-2-(二甲氨基)丙醇，通过氯化(R)-2-(二甲氨基)丙醇形成(R)-1-氯-N,N-二甲基丙烷-2-胺盐酸盐，通过混合(R)-1-氯-N,N-二甲基丙烷-2-胺盐酸盐和二苯基乙腈与钾叔丁氧化物合成左旋美沙酮腈盐酸盐，通过将左旋美沙酮腈盐酸盐暴露于格氏试剂生成左旋美沙酮盐酸盐。