羟基1-(3-氯苯基)-2-[(1,1-二甲基乙基)氨基]-1-丙酮盐酸盐 | 357399-43-0

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 羟基1-(3-氯苯基)-2-[(1,1-二甲基乙基)氨基]-1-丙酮盐酸盐
• 中文别名: 安非他酮吗啉醇；安非他酮吗啉代杂质
• 英文名称: (2R,3R)-2-(-3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol
• 英文别名: (+/-)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol；2-hydroxybupropion；hydroxybupropion；2-Hydroxy-2-(3'-chlorophenyl)-3,5,5-trimethylmorpholine；HBUP；HB；Hydroxy Bupropion；2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
• CAS: 357399-43-0
• 化学式: C₁₃H₁₈ClNO₂
• 分子量: 255.744
• InChiKey: RCOBKSKAZMVBHT-UHFFFAOYSA-N

物化性质

• 熔点：
  121-123°C
• 沸点：
  386.6±42.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：20 mg/ml； DMSO：20 mg/ml；乙醇：20 mg/ml；乙醇:PBS(pH 7.2) (1:1): 0.50 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  羟基1-(3-氯苯基)-2-[(1,1-二甲基乙基)氨基]-1-丙酮盐酸盐 生成 (+)-(2S,3S)-2-(3-氯苯基)-3,5,5-三甲基吗啉-2-醇
  参考文献：
  名称：

  Pharmaceutically active morpholinol

  摘要：

  本发明公开了化合物（+）-（2S,3S）-2-（3-氯苯基）-3,5,5-三甲基-2-吗啡啡醇及其药学上可接受的盐和溶剂化物，包括它们的制药组合物；还公开了使用该化合物、盐、溶剂化物或组合物治疗抑郁症、注意力缺陷多动障碍（ADHD）、肥胖症、偏头痛、疼痛、性功能障碍、帕金森病、阿尔茨海默病或对可卡因或含尼古丁（特别是烟草）产品上瘾的方法。

  公开号：

  US06391875B2
• 作为产物：
  描述：

  3'-氯丙酮苯 在 溴 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 0.83h， 生成 羟基1-(3-氯苯基)-2-[(1,1-二甲基乙基)氨基]-1-丙酮盐酸盐
  参考文献：
  名称：

  Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6β-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents

  摘要：

  A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated clogP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.06.018

文献信息

• Enhancing transdermal delivery of opiod antagonists and agonistis using codrugs links to bupropion or hydroxybupropion
  申请人：Stinchcomb Audra L.

  公开号：US20090017102A1

  公开（公告）日：2009-01-15

  The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist.

  本发明涉及新颖的共药物，包括由化学键连接的丁丙诺啡或羟基丁丙诺啡与阿片类拮抗剂或阿片类激动剂。与基本的阿片类拮抗剂或阿片类激动剂相比，这些共药物在人类皮肤上的透皮通量有显著提高。
• [EN] ENZYME-CATALYZED DYNAMIC KINETIC RESOLUTION PROCESS FOR PREPARING (+)-(2S, 3S)-2-(3-CHLOROPHENYL)-3,5,5-TRIMETHYL-2-MORPHOLINOL, SALTS, AND SOLVATES THEREOF<br/>[FR] PROCEDE DE RESOLUTION CINETIQUE DYNAMIQUE CATALYSEE PAR DES ENZYMES PERMETTANT DE PREPARER DU (+)-(2S, 3S)-2-(3-CHLOROPHENYL)-3,5,5-TRIMETHYL-2-MORPHOLINOL, DES SELS ET DES SOLVATES DE CE DERNIER
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005042503A1

  公开（公告）日：2005-05-12

  A process for preparing (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol, pharmaceutically acceptable salts and solvates thereof such as the (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride salt via enzyme-catalyzed dynamic kinetic resolutions is provided.

  提供一种通过酶催化动力学拆分制备(+)-(2S, 3S)-2-(3-氯苯基)-3,5,5-三甲基-2-吗啉醇、其药用盐和溶剂结晶物，例如(+)-(2S, 3S)-2-(3-氯苯基)-3,5,5-三甲基-2-吗啉醇盐酸盐的方法。
• Bupropion metabolites and methods of use
  申请人：Sepracor, Inc.

  公开号：US06337328B1

  公开（公告）日：2002-01-08

  Methods are disclosed which utilize metabolites of bupropion for treating sexual dysfunction.

  揭示了利用安非他酮代谢物治疗性功能障碍的方法。
• [EN] BUPROPION METABOLITES AND METHODS OF THEIR SYNTHESIS AND USE<br/>[FR] METABOLITES DU BUPROPION ET LEURS PROCEDES DE SYNTHESE ET D'UTILISATION
  申请人：SEPRACOR INC

  公开号：WO2001062257A2

  公开（公告）日：2001-08-30

  Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

  本发明公开了利用丁丙腈代谢物治疗神经元单胺再摄取抑制改善的疾病的方法和组合物。这些疾病包括但不限于性功能障碍、情感障碍、脑功能障碍、吸烟和失禁。本发明还公开了制备光学纯丁丙腈代谢物的方法。
• [EN] PHARMACEUTICALLY ACTIVE MORPHOLINOL<br/>[FR] MORPHOLINOL PHARMACEUTIQUEMENT ACTIF
  申请人：GLAXO GROUP LIMITED

  公开号：WO1999037305A1

  公开（公告）日：1999-07-29

  (EN) Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions comprising them; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, pain, sexual dysfunction, Parkinson's disease, Alzheimer's disease, or addiction to cocaine or nicotine-containing (especially tobacco) products using such compound, salts, solvates or compositions.(FR) La présente invention concerne le composé (+)-(2S,3S)-2-(3-chlorophényle)-3,5,5-triméthyle-2-morpholinol, les sels et les solvats pharmaceutiquement acceptables de ce composé ainsi que des compositions renfermant lesdites substances. L'invention concerne également une méthode de traitement, au moyen desdits composés, sels, solvats et compositions, de la dépression, des troubles de l'hyperactivité avec déficit de l'attention, de l'obésité, de la migraine, de la douleur, des dysfonctionnements sexuels, de la maladie de Parkinson, de la maladie d'Alzheimer et de la dépendance à la cocaïne ou aux produits renfermant de la nicotine (en particulier le tabac).

  揭示了化合物(+)-(2S,3S)-2-(3-氯苯基)-3,5,5-三甲基-2-吗啉醇及其药学上可接受的盐和溶剂化物，包括它们的制药组合物；还揭示了使用这种化合物、盐、溶剂化物或组合物治疗抑郁症、注意力缺陷多动障碍（ADHD）、肥胖症、偏头痛、疼痛、性功能障碍、帕金森病、阿尔茨海默病或对可卡因或含尼古丁（尤其是烟草）产品上瘾的方法。