(S)-methadone hydrochloride | 15284-15-8

• 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: (S)-methadone hydrochloride
• 英文别名: (S)-6-(dimethylamino)-4,4-diphenyl-3-heptanone hydrochloride；(+)-Methadone hydrochloride；(6S)-6-(dimethylamino)-4,4-diphenylheptan-3-one;hydrochloride
• CAS: 15284-15-8
• 化学式: C₂₁H₂₇NO*ClH
• 分子量: 345.912
• InChiKey: FJQXCDYVZAHXNS-LMOVPXPDSA-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：

  (S)-methadone hydrochloride 在 sodium tetrahydroborate 、 cerium(III) chloride 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以100%的产率得到(3S,6S)-Methadol
  参考文献：
  名称：

  Synthesis of optically active methadones, LAAM and bufuralol by lipase-catalysed acylations

  摘要：

  (R)- and (S)-Methadones and levo-alpha-acetylmethadol (LAAM) have been synthesised starting from lipase-catalysed acylation of dimethylaminopropan-2-ol. An approach to the synthesis of (R)-bufuralol is also presented. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(03)00019-3
• 作为产物：
  描述：

  盐酸美沙酮 在 盐酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲基叔丁基醚 、 水 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 (S)-methadone hydrochloride
  参考文献：
  名称：

  Non-Racemic Mixtures of Various Ratios of D- and L-methadone and Methods of Treating Pain Using the Same

  摘要：

  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。

  公开号：

  US20160235691A1

文献信息

• [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 OR DEXTROMETHADONE HYDROCHLORIDE AND METHODS FOR USE THEREOF
  申请人：Cody Laboratories, Inc.

  公开号：US20190002394A1

  公开（公告）日：2019-01-03

  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.

  提供了高效的方法，从D-丙氨酸或L-丙氨酸开始合成左甲烷麻黄定盐酸盐或右甲烷麻黄定盐酸盐，保持构型。提供了治疗主体的方法，包括给予含有效量左甲烷麻黄定盐酸盐的组合物，其中右甲烷麻黄定盐酸盐的含量不超过10 ppm。
• Synthesis of levomethadone hydrochloride or dextromethadone hydrochloride and methods for use thereof
  申请人：Cody Laboratories, Inc.

  公开号：US10040752B2

  公开（公告）日：2018-08-07

  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.

  提供了分别从 D-丙氨酸或 L-丙氨酸开始合成盐酸左美沙酮或盐酸右美沙酮的高效方法，并保留了构型。提供了治疗受试者的方法，包括施用一种组合物，该组合物包含有效量的盐酸左美沙酮，其右美沙酮含量不超过 10 ppm。
• Pharmaceutical composition and method for treating disorders of the central nervous system
  申请人：Galer S Bradley

  公开号：US20060167032A1

  公开（公告）日：2006-07-27

  Disorders of the ventral nervous system (CNS) are treated by the administration of a GABA analog such as gabapentin or pregablin, an NMDA receptor antagonist such as dextromethorphan or d-methodone and, optionally, another pharmacologically active substance, e.g., one which is effective for the treatment of a CNS disorder.

  治疗腹侧神经系统（CNS）疾病的方法是服用 GABA 类似物（如加巴喷丁或普瑞巴林）、NMDA 受体拮抗剂（如右美沙芬或 d-美托咪酮）以及另一种药理活性物质（如对治疗 CNS 疾病有效的物质）。