(2S,3S)-3-(3,4-Dichloro-phenyl)-2-methoxycarbonyl-8-methyl-8-azonia-bicyclo[3.2.1]octane

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: (2S,3S)-3-(3,4-Dichloro-phenyl)-2-methoxycarbonyl-8-methyl-8-azonia-bicyclo[3.2.1]octane
• 英文别名: methyl (2S,3S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• 化学式: C₁₆H₁₉Cl₂NO₂
• 分子量: 328.2
• InChiKey: AMIHUYQKNJHXPT-XNSJETLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• COCAINE RECEPTOR BINDING LIGANDS
  申请人：KUHAR Michael J.

  公开号：US20080153870A1

  公开（公告）日：2008-06-26

  A class of binding ligands for cocaine receptors and other receptors in the brain. Specifically, a novel family of compounds shows high binding specificity and activity, and, in a radiolabeled form, can be used to bind to these receptors, for biochemical assays and imaging techniques. Such imaging is useful for determining effective doses of new drug candidates in human populations. In addition, the high specificity, slow onset and long duration of the action of these compounds at the receptors makes them particularly well suited for therapeutic uses, for example as substitute medication for psychostimulant abuse. Some of these compounds may be useful in treating Parkinson's Disease or depression, by virtue of their inhibitory properties at monoamine transporters.

  一类可与可卡因受体和其他脑部受体结合的配体。具体而言，一种新型化合物家族表现出高结合特异性和活性，并且在放射性标记形式下，可用于结合这些受体进行生化分析和成像技术。这种成像有助于确定新药候选物在人群中的有效剂量。此外，这些化合物在受体上的高特异性、缓慢的起效时间和长效作用使它们特别适合于治疗用途，例如作为精神刺激物滥用的替代药物。其中一些化合物可能通过其在单胺转运体上的抑制作用，在治疗帕金森病或抑郁症方面具有用处。
• POTENT AND SELECTIVE INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF
  申请人：THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH AND HUMAN SERVICE

  公开号：US20160009644A1

  公开（公告）日：2016-01-14

  Disclosed herein are bisarylmethylthioacetamides and bisarylmethylthioethylamines useful as inhibitors of monoamine transporters. The compounds are potent and/or selective inhibitors of dopamine (DA), serotonin (5-HT), and/or norepinephrine (NE) reuptake via their respective transporters, DAT, SERT and NET. Also disclosed are methods for eliciting a wake-promoting or cognitive or attention enhancing effect and for treating substance use disorders, attention deficit (hyperactivity) disorder, depressive disorders, bipolar disorder or other neuropsychiatric disorders sleep disorders or cognitive impairment using the compounds.

  本文揭示了双芳基甲硫基乙酰胺和双芳基甲硫基乙胺作为单胺转运体抑制剂的用途。这些化合物是通过它们各自的转运体DAT、SERT和NET对多巴胺（DA）、5-羟色胺（5-HT）和/或去甲肾上腺素（NE）的再摄取具有强效和/或选择性抑制作用。还揭示了利用这些化合物引发促醒、认知或注意力增强效应以及治疗物质使用障碍、注意缺陷（多动）障碍、抑郁障碍、双相障碍或其他神经精神障碍、睡眠障碍或认知障碍的方法。
• Cocaine receptor binding ligands
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：EP0905135A2

  公开（公告）日：1999-03-31

  Novel compounds show high affinity for specific cocaine receptors in the brain, particularly dopamine transporter sites, and have the formula Wherein Y = CH2R3, CO2R2 or R1 =hydrogen, C1-5 alkyl, R2 =hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-6 alkynyl, halogen or amine, R3 =OH, hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, Cl, Br, I, CN, NH2, NHC1-6 alkyl, NC1-6 alkyl, OCOC1-6 alkyl, OCOC1-3 alkylaryl, A =S, O or NH X =H, C1-6 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, C1-6 alkynyl, halogen, amino, acylamido, and Z =H, I, Br, Cl, F, CN, CF3 NO2, N3, OR1, CO2NH2, CO2R1, C1-6 alkyl, NR4R5, NHCOR5, NHCO2R6, wherein R4-R6 are each C1-6 alkyl.

  新型化合物对大脑中的特定可卡因受体，特别是多巴胺转运体位点具有高亲和力，其分子式为 其中 Y = CH2R3、CO2R2 或 R1 = 氢、C1-5 烷基、 R2 = 氢、C1-6 烷基、C3-8 环烷基、C1-4 烷氧基、C1-6 烷炔基、卤素或胺、 R3 =OH、氢、C1-6 烷基、C3-8 环烷基、C1-4 烷氧基、Cl、Br、I、CN、NH2、NHC1-6 烷基、NC1-6 烷基、OCOC1-6 烷基、OCOC1-3 烷芳基、 A =S、O 或 NH X =H、C1-6 烷基、C3-8 环烷基、C1-4 烷氧基、C1-6 烷炔基、卤素、氨基、酰氨基、 和 Z =H、I、Br、Cl、F、CN、CF3 NO2、N3、OR1、CO2NH2、CO2R1、C1-6 烷基、NR4R5、NHCOR5、NHCO2R6、 其中 R4-R6 各为 C1-6 烷基。
• Intermediates for the synthesis of radiolabelled tropanes
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：EP1238978A2

  公开（公告）日：2002-09-11

  The compounds of the present invention comprise a tropane compound or ligand that selectively binds to tropane recognition sites, e.g., neuron transporters such as that DAT. The tropane ligand is radiolabeled with a radioactive technetium or rhenium by a chelating ligand which is attached to the tropane ligand by a linker. Tropane compounds or ligands useful in the pratice of the present invention can generally be represented by formula II where R1 and R2 are defined as above and where R1 can also be substituted at the C4 position of the tropane ring: Any tropane compound of the general formula II is useful in the present invention so long as it binds to DAT. Useful tropane analogs have a 3α-group,i.e., are of the boat configuration. Intermediates for the synthesis of the radiolabeled tropanes are claimed.

  本发明的化合物包括一种选择性地结合到对氮杂环戊烷识别位点（如神经元转运体，如 DAT）的对氮杂环戊烷化合物或配体。通过螯合配体对托烷配体进行放射性锝或铼标记，螯合配体通过连接体连接到托烷配体上。 在本发明实践中有用的托烷化合物或配体一般可用式 II 表示，其中 R1 和 R2 的定义如上，R1 也可以在托烷环的 C4 位被取代： 只要能与 DAT 结合，通式 II 的任何托烷化合物在本发明中都是有用的。 有用的托烷类似物具有 3α 基团，即具有舟形构型。本发明要求合成放射性标记的托烷的中间体。
• Potent and selective inhibitors of monoamine transporters; method of making; and use thereof
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary, Department of Health and Human Services, Office of Technology Transfer, National Institutes of Health

  公开号：US10590074B2

  公开（公告）日：2020-03-17

  Disclosed herein are bisarylmethylthioacetamides and bisarylmethylthioethylamines useful as inhibitors of monoamine transporters. The compounds are potent and/or selective inhibitors of dopamine (DA), serotonin (5-HT), and/or norepinephrine (NE) reuptake via their respective transporters, DAT, SERT and NET. Also disclosed are methods for eliciting a wake-promoting or cognitive or attention enhancing effect and for treating substance use disorders, attention deficit (hyperactivity) disorder, depressive disorders, bipolar disorder or other neuropsychiatric disorders sleep disorders or cognitive impairment using the compounds.

  本文公开了可用作单胺转运体抑制剂的双芳基甲硫基乙酰胺和双芳基甲硫基乙胺。这些化合物是多巴胺（DA）、5-羟色胺（5-HT）和/或去甲肾上腺素（NE）通过各自的转运体 DAT、SERT 和 NET 再摄取的强效和/或选择性抑制剂。此外，还公开了利用这些化合物激发促进觉醒或认知或注意力增强效应以及治疗药物使用障碍、注意力缺陷（多动）症、抑郁症、双相情感障碍或其他神经精神疾病睡眠障碍或认知障碍的方法。