dextrorphan

• 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: dextrorphan
• 英文别名: levorphanol；Dextrorphan, Antibiotic for Culture Media Use Only；(1S,9S)-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-ol
• 化学式: C₁₇H₂₃NO
• 分子量: 257.376
• InChiKey: JAQUASYNZVUNQP-HGVHAKBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  dextrorphan 在 双氧水 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Groutas, W.C.; Essawi, M.; Portoghese, P.S., Synthetic Communications, 1980, vol. 10, # 7, p. 495 - 502

  摘要：

  DOI：
• 作为产物：
  描述：

  右美沙芬 在 cytochrome P₄₅₀ 2D₆ enzyme 作用下， 反应 0.1h， 生成 dextrorphan
  参考文献：
  名称：

  CYP2D6 Allelic Variants *34, *17-2, *17-3, and *53 and a Thr309Ala Mutant Display Altered Kinetics and NADPH Coupling in Metabolism of Bufuralol and Dextromethorphan and Altered Susceptibility to Inactivation by SCH 66712

  摘要：

  代谢表型可能受到多种因素的影响，包括等位基因变异和与抑制剂的相互作用。人类 CYP2D6 负责约 20% 的细胞色素 P450 介导的药物代谢，但由 100 多种已知变体组成；几种变体在人群中很常见，而其他变体则相当罕见。四种 CYP2D6 等位基因变体 - 三种在活性位点远端具有一系列突变（*34、*17-2、*17-3），一种超代谢型在活性位点附近具有突变（*53），以及参考* 1 和 *1 的活性位点突变体 (Thr309Ala) 被表达、纯化，并研究了与典型底物右美沙芬和布呋洛尔以及灭活剂 SCH 66712 的相互作用。我们发现 *34、*17-2 和 *17- 3 显示酶活性和 NADPH 偶联降低，同时产生与 *1 相同的代谢物，表明 Arg296 在 NADPH 偶联中可能发挥作用。较高活性的变体 *53 表现出与 *1 相似的 NADPH 偶联，但不太容易被 SCH 66712 失活。Thr309Ala 突变体表现出与 *1 相似的活性，但 NADPH 偶联大大降低。总体而言，这些结果表明需要对单个 CYP2D6 变体进行动力学和代谢分析，以了解它们对可变药物反应和个性化医疗的复杂性的可能贡献。

  DOI：

  10.1124/dmd.117.079871

文献信息

• COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESPIRATORY DISORDERS
  申请人：Kandula Mahesh

  公开号：US20150087670A1

  公开（公告）日：2015-03-26

  The invention relates to the compounds of formula I 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, and methods for the treatment of respiratory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold), as well as those resulting from inhaled particle irritants, upper respiratory infections, (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis, neuropathic pain and pain associated with fibromyalgia.

  本发明涉及公式I的化合物或其药用可接受的盐，以及它们的 polymorphs（多晶型）、solvates（溶剂合物）、enantiomers（对映体）、stereoisomers（立体异构体）和 hydrates（水合物）。包含有效量的公式I化合物的药物组合物，以及用于治疗呼吸系统疾病的方法，可以口服、颊部、直肠、局部、经皮、经粘膜、静脉内、非肠道给药、糖浆或注射等方式制备。此类组合物可用于治疗由轻微喉咙和支气管刺激引起的咳嗽（例如常见于流感和普通感冒时），以及由吸入颗粒刺激物、上呼吸道感染、肌萎缩侧索硬化症和多发症患者的（假性球麻痹）以及神经性疼痛和纤维肌痛相关的疼痛。
• TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS
  申请人：Alkermes, Inc.

  公开号：US20160243112A1

  公开（公告）日：2016-08-25

  The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound-1, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种用于治疗阿尔茨海默病患者的神经精神行为症状的方法，其中所述症状选自焦虑、激动、攻击性、抑郁、幻觉、记忆丧失、混乱、重复、睡眠问题、日落综合征、怀疑、妄想和漫游的组，包括向患者施用有效量的公式I、IA、IB、表1中的化合物，优选化合物-1或其药用可接受的盐。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF RESPIRATORY DISORDERS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE TROUBLES RESPIRATOIRES
  申请人：KANDULA MAHESH

  公开号：WO2013168012A1

  公开（公告）日：2013-11-14

  The invention relates to the compounds of formula (I) 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), and methods for the treatment of respiratory disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold), as well as those resulting from inhaled particle irritants, upper respiratory infections, (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis, neuropathic pain and pain associated with fibromyalgia.

  本发明涉及公式(I)化合物或其药用可接受盐，以及它们的聚合物、溶剂化物、对映异构体、立体异构体和水合物。包含有效量的公式(I)化合物的药物组合物，以及用于治疗呼吸系统疾病的方法，可以口服、颊部、直肠、局部、经皮、经粘膜、静脉、非肠道给药、糖浆或注射的剂型。此类组合物可用于治疗由小喉咙和支气管刺激引起的咳嗽（如通常伴随流感和普通感冒），以及由吸入颗粒刺激物、上呼吸道感染、肌萎缩侧索硬化症和多发症患者的（假性球麻痹）以及神经性疼痛和纤维肌痛相关的疼痛。
• LOCAL ANESTHETIC COMPOSITIONS CONTAINING DEXTROROTATORY MORPHINAN DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：WANG JHI-JOUNG

  公开号：US20080070939A1

  公开（公告）日：2008-03-20

  Dextrorotatory morphinan derivatives of formula (I) or pharmaceutically acceptable salts thereof were found to have local anesthetic effects: wherein R and R′ are independently selected from hydrogen and a methyl group, and at least one of R and R′ is a methyl group. The dextrorotatory morphinan derivatives of formula (I) or pharmaceutically acceptable salts thereof can therefore be used in the manufacture of pharmaceutical compositions for local anesthesia that may provide a safe and prolonged local anesthetic effect.
• PHARMACEUTICAL COMPOSITIONS COMPRISING DEXTROMETHORPHAN AND QUINIDINE FOR THE TREATMENT OF DEPRESSION, ANXIETY, AND NEURODEGENERATIVE DISORDERS
  申请人：Berg James

  公开号：US20090111846A1

  公开（公告）日：2009-04-30

  Pharmaceutical compositions and methods for treating depression, anxiety, and neurodegenerative diseases and cognitive disorders, such as dementia and Alzheimer's disease, by administering same are provided. The compositions comprise dextromethorphan in combination with quinidine.