(4bS,8aS,9S)-11-methyl-3-(trifluoromethoxy)-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene | 1044833-36-4

• 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: (4bS,8aS,9S)-11-methyl-3-(trifluoromethoxy)-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene
• 英文别名: (1S,9S,10S)-17-methyl-4-(trifluoromethoxy)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene
• CAS: 1044833-36-4
• 化学式: C₁₈H₂₂F₃NO
• 分子量: 325.374
• InChiKey: NMJZWYOBPYDTML-PVAVHDDUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-去甲右美沙芬 在 lithium aluminium tetrahydride 、 4-叔丁基-2,6-二甲基苯基三氟化硫 、 三氯化锑 、 三溴化硼 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.17h， 生成 (4bS,8aS,9S)-11-methyl-3-(trifluoromethoxy)-6,7,8,8a,9,10-hexahydro-5H-9,4b-(epiminoethano)phenanthrene
  参考文献：
  名称：

  代谢不稳定的含芳基甲基醚的天然产物的后期转化为氟代烷基类似物。

  摘要：

  我们报告了通过天然产物衍生的FDA批准的治疗剂的后期功能化将芳基甲基醚和苯酚转化为六个氟代烷基类似物。这一系列简短的合成序列利用了现代方法和传统方法的结合，并证明了一些最近报道的方法在像天然产物的支架上的作用并不总是如期望的那样。尽管如此，为了药物化学目的，反应优化可以递送足够量的每种目标类似物。在某些情况下，经典反应和合成序列仍胜过现代有机氟转化，这应鼓励继续寻求改进的反应。总体，

  DOI：

  10.1021/acs.joc.0c00125

文献信息

• COMBINATION OF MORPHINAN COMPOUNDS AND ANTIDEPRESSANT FOR THE TREATMENT OF PSEUDOBULBAR AFFECT, NEUROLGICAL DISEASES, INTRACTABLE AND CHRONIC PAIN AND BRAIN INJURY
  申请人：Concert Pharmaceuticals, Inc.

  公开号：US20160143902A1

  公开（公告）日：2016-05-26

  Provided herein are compositions comprising a dextromethorphan analog according to Formula I or Formula II or a pharmaceutically acceptable salt thereof of either of the foregoing, and a co-agent, e.g., an antidepressant such as a serotonin norepinephrine reuptake inhibitor; a serotonin noradrenaline dopamine reuptake inhibitor; a norepinephrine dopamine reuptake inhibitor; a monoamine oxidase inhibitor; a selective serotonin reuptake inhibitor; and a tricyclic antidepressant or a pharmaceutically acceptable salt of any of the foregoing. The compositions are useful in the the treatment of pseudobulbar affect, neuropathic pain, neurodegenerative diseases, brain injuries, and the like.

  本文提供了包含根据公式I或公式II的右美沙芬类似物或其药学上可接受的盐之一，以及辅助剂，例如抗抑郁药物，如选择性5-羟色胺和去甲肾上腺素再摄取抑制剂；5-羟色胺、去甲肾上腺素、多巴胺再摄取抑制剂；去甲肾上腺素、多巴胺再摄取抑制剂；单胺氧化酶抑制剂；选择性5-羟色胺再摄取抑制剂；三环抗抑郁药物或其中任何一种的药学上可接受的盐的组合物。这些组合物在假性球麻痹、神经痛、神经退行性疾病、脑损伤等治疗中非常有用。
• COMBINATION OF MORPHINAN COMPOUNDS AND ANTIDEPRESSANT FOR THE TREATMENT OF PSEUDOBULBAR AFFECT, NEUROLOGICAL DISEASES, INTRACTABLE AND CHRONIC PAIN AND BRAIN INJURY
  申请人：CONCERT PHARMACEUTICALS, INC.

  公开号：EP3090760A1

  公开（公告）日：2016-11-09

  Provided herein are compositions comprising a dextromethorphan analog according to Formula II or a pharmaceutically acceptable salt thereof, and a co-agent which is norepinephrine-dopamine reuptake inhibitor (NDRI) or a pharmaceutically acceptable salt thereof. The compositions are use ful in the treatment of pseudobulbar affect, neuropathic pain, neurological disorders, brain injuries and the like:

  本文提供的组合物包含符合式 II 的右美沙芬类似物或其药学上可接受的盐，以及去甲肾上腺素-多巴胺再摄取抑制剂（NDRI）或其药学上可接受的盐。这些组合物可用于治疗假性肺水肿、神经性疼痛、神经系统疾病、脑损伤等：
• Fluoroalkylation of Dextromethorphan Improves CNS Exposure and Metabolic Stability
  作者：Jacob P. Sorrentino、Ryan A. Altman

  DOI：10.1021/acsmedchemlett.2c00055

  日期：2022.4.14
• PHARMACEUTICAL COMPOSITIONS COMPRISING A DEXTROMETHORPHAN COMPOUND AND QUINIDINE FOR THE TREATMENT OF AGITATION IN DEMENTIA
  申请人：AVANIR PHARMACEUTICALS, INC.

  公开号：US20190111047A1

  公开（公告）日：2019-04-18

  The present disclosure is related to methods of treating agitation and/or aggression and/or associated symptoms in subjects with dementia, including, dementia associated with Alzheimer's disease. The method includes administering to a subject in need thereof a dextromethorphan compound, or a pharmaceutically acceptable salt thereof, in combination with quinidine, or a pharmaceutically acceptable salt thereof. The disclosure in certain aspects is also related to compositions that are used for treating agitation and/or aggression and/or associated symptoms in subjects suffering from Alzheimer's disease.
• COMPOSITIONS AND METHODS THEREOF
  申请人：Vepachedu Sreenivasarao

  公开号：US20190183885A1

  公开（公告）日：2019-06-20

  Compounds of Formula I: or enantiomers thereof, metabolites thereof, derivatives thereof, deuterated derivatives thereof, prodrugs thereof, pharmaceutically acceptable salts thereof, N-oxides thereof, or a combination thereof, processes and intermediates for preparation thereof, compositions thereof, and uses thereof, are provided. Pharmaceutical compositions comprising a compound of formula I and a compound of Formula II: or enantiomers thereof, metabolites thereof, derivatives thereof, deuterated derivatives thereof, prodrugs thereof, pharmaceutically acceptable salts thereof, N-oxides thereof, or a combination thereof. Compositions and methods for improving the efficacy of DEX, or providing beneficial pharmacokinetic effects to DEX, comprising co-administering a compound of formula I or SARPO, and a compound of Formula II or DEX to a subject in need thereof, and dosage forms, drug delivery systems, methods of treatment thereof.