(1R,2S,3S,5S)-3-(3,4-二氯苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 | 146725-34-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (1R,2S,3S,5S)-3-(3,4-二氯苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯
• 英文名称: 3β-(3,4-dichlorophenyl)-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester
• 英文别名: methyl (1R,2S,3S,5S)-3-(3,4-dichlorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate；O-456；Dichloropane
• CAS: 146725-34-0
• 化学式: C₁₅H₁₇Cl₂NO₂
• 分子量: 314.211
• InChiKey: JFUNLJPTPCQLIR-PJQZNRQZSA-N

物化性质

• 沸点：
  407.6±45.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,5S)-3-(3,4-二氯苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 在 potassium carbonate 、 N,N-二异丙基乙胺 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.5h， 生成 2-(3-sec-butylimino-6-diethylamino-3H-xanthen-9-yl)-5-[(4-{2-[3β-(3,4-dichlorophenyl)-2β-methoxycarbonyl-8-aza-bicyclo[3.2.1]oct-8-yl]ethylcarbamoyl}cyclohexylmethyl)sulfamoyl]benzenesulfonic acid anion
  参考文献：
  名称：

  Rhodamine-Labeled 2β-Carbomethoxy-3β-(3,4-dichlorophenyl)tropane Analogues as High-Affinity Fluorescent Probes for the Dopamine Transporter

  摘要：

  Novel fluorescent ligands were synthesized to identify a high-affinity probe that would enable visualization of the dopamine transporter (DAT) in living cells. Fluorescent tags were extended from the N- or 2-position of 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane, using an ethylamino linker. The resulting 2-substituted (5) and N-substituted (9) rhodamine-labeled ligands provided the highest DAT binding affinities expressed in COS-7 cells (K-i = 27 and 18 nM, respectively) in the series. Visualization of the DAT with 5 and 9 was demonstrated by confocal fluorescence laser scanning microscopy in stably transfected HEK293 cells.

  DOI：

  10.1021/jm050431y
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 溶剂黄146 、 三氟乙酸 、 锌 作用下， 反应 29.25h， 生成 (1R,2S,3S,5S)-3-(3,4-二氯苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯
  参考文献：
  名称：

  Synthesis of iodinated and radioiodinated (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(3′,4′-dichlorophenyl) nortropane (β-CDIT): a ligand for the dopamine transporter

  摘要：

  The synthesis of (E)-N-(3-iodoprop-2-enyl)-2 beta-carbomethoxy-3 beta-(3', 4'-dichiorophenyl) nortropane (beta-CDIT) and its radioiodinated analogues is described. Three different synthetic methods are reported for the preparation of (E)-N-[3-(tributylstannyl)-2-enyl]-2 beta carbomethoxy-3 beta-(3', 4'-dichlorophenyl) nortropane, which was iododestannylated for the preparation of the corresponding iodinated derivative. We also report the radiolabelling of beta-CDIT with I-125 Or I-123 that could be used for in vitro and in vivo exploration of the dopamine transporter.

  DOI：

  10.1002/(sici)1099-1344(199709)39:9<757::aid-jlcr24>3.0.co;2-j

文献信息

• Chemical Targeting of Voltage Sensitive Dyes to Specific Cells and Molecules in the Brain
  作者：Tomas Fiala、Jihang Wang、Matthew Dunn、Peter Šebej、Se Joon Choi、Ekeoma C. Nwadibia、Eva Fialova、Diana M. Martinez、Claire E. Cheetham、Keri J. Fogle、Michael J. Palladino、Zachary Freyberg、David Sulzer、Dalibor Sames

  DOI：10.1021/jacs.0c00861

  日期：2020.5.20

  dense dopaminergic axons in the mouse striatum and sparse noradrenergic axons in the mouse cortex in acute brain slices. PFQX in conjunction with ligand-directed acyl imidazole chemistry enables covalent labeling of AMPA-type glutamate receptors in the same brain regions. Probe variants bearing either a classical electrochromic ANEP dye or state-of-the-art VoltageFluor-type dye respond to membrane potential

  电压敏感荧光染料 (VSD) 是探测神经元和其他可兴奋细胞中信号转导的重要工具。然而，由于在脑组织或活体动物中缺乏细胞特异性靶向方法，这些高度亲脂性传感器的影响受到限制。我们通过引入非遗传分子平台来解决这一关键挑战，用于大脑中合成 VSD 的细胞和分子特异性靶向。我们采用葡聚糖聚合物颗粒，通过动态封装和高亲和力配体克服 VSD 固有的亲脂性，仅在生理表达水平上利用神经传递机制的天然成分将构建体靶向特定神经元细胞。二氯烷，一种单胺转运蛋白配体，能够靶向小鼠纹状体中密集的多巴胺能轴突和急性脑切片中小鼠皮层中稀疏的去甲肾上腺素能轴突。PFQX 与配体导向的酰基咪唑化学相结合，能够在相同的大脑区域中对 AMPA 型谷氨酸受体进行共价标记。带有经典电致变色 ANEP 染料或最先进的电压氟型染料的探针变体以与母体染料类似的方式响应膜电位变化，如全细胞贴片记录所示。我们用单光子和双光子荧光显微镜证明了用
• Intermediates for the synthesis of radiolabelled tropanes
  申请人：PRESIDENT AND FELLOWS OF HARVARD COLLEGE

  公开号：EP1238978A3

  公开（公告）日：2005-03-02

  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 the 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特定结合到特罗班识别位点的特罗班化合物或配体，例如神经元转运体如DAT。特罗班配体通过连接剂连接到特罗班配体的螯合配体上，用放射性锝或铼进行放射标记。本发明实施中有用的特罗班化合物或配体通常可用以下公式表示，其中R1和R2如上定义，且R1也可取代于特罗班环的C4位置：只要结合到DAT，任何符合上述一般公式II的特罗班化合物在本发明中均有用。有用的特罗班类似物具有3α-基团，即处于船状构型。本发明要求合成放射标记特罗班的中间体。
• Novel Fluorescent Ligands Enable Single-Molecule Localization Microscopy of the Dopamine Transporter
  作者：Daryl A. Guthrie、Carmen Klein Herenbrink、Matthew Domenic Lycas、Therese Ku、Alessandro Bonifazi、Brian T. DeVree、Signe Mathiasen、Jonathan A. Javitch、Jonathan B. Grimm、Luke Lavis、Ulrik Gether、Amy Hauck Newman

  DOI：10.1021/acschemneuro.0c00397

  日期：2020.10.21

  transporter (DAT) is critical for spatiotemporal control of dopaminergic neurotransmission and is the target for therapeutic agents, including ADHD medications, and abused substances, such as cocaine. Here, we develop new fluorescently labeled ligands that bind DAT with high affinity and enable single-molecule detection of the transporter. The cocaine analogue MFZ2-12 (1) was conjugated to novel rhodamine-based

  多巴胺转运蛋白 (DAT) 对于多巴胺能神经传递的时空控制至关重要，并且是治疗药物（包括 ADHD 药物）和滥用物质（如可卡因）的目标。在这里，我们开发了新的荧光标记配体，以高亲和力结合 DAT，并能够对转运蛋白进行单分子检测。可卡因类似物 MFZ2-12 ( 1 ) 与新型基于罗丹明的 Janelia 荧光团（JF 549和 JF 646）结合。所得配体与 DAT 的高亲和力结合通过 [ 3H] 多巴胺在 DAT 转染的 CAD 细胞中的摄取和通过在大鼠纹状体膜上进行的竞争性放射性配体结合实验。结合的可视化通过共聚焦或 TIRF 显微镜证实，揭示类似物与 DAT 转染的 CAD 细胞的选择性结合。使用 JF 549偶联的 DG3-80 ( 3 ) 和 JF 646偶联的 DG4-91 ( 4 ) 在 DAT 转染的 CAD 细胞上进行单粒子跟踪实验，从而能够将 DAT 的动态行为量化和分类为四个不同的运动类别（固定的）。
• Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types
  申请人：Nlife Therapeutics S.L.

  公开号：EP2380595A1

  公开（公告）日：2011-10-26

  The invention provides a conjugate comprising (i) a nucleic acid which is complementary to a target nucleic acid sequence and which expression prevents or reduces expression of the target nucleic acid and (ii) a selectivity agent which is capable of binding with high affinity to a neurotransmitter transporter. The conjugates of the present invention are useful for the delivery of the nucleuc acid toi cell of interests and thus, for the treatment of diseases which require a down-regulation of the protein encoded by the target nucleic acid as well as for the delivery of contrast agents to the cells for diagnostic purposes.

  本发明提供了一种共轭物，该共轭物包含(i)与靶核酸序列互补的核酸，该核酸的表达可防止或减少靶核酸的表达；(ii)能够与神经递质转运体高亲和力结合的选择剂。本发明的共轭物可用于将核酸递送至相关细胞，从而治疗需要下调靶核酸编码蛋白的疾病，也可用于将造影剂递送至细胞以进行诊断。
• NMN AND DERIVATIVES FOR ITS USE IN THE TREATMENT OF DEPRESSION AND/OR ANXIETY IN PATIENTS HAVING A FORM OF PARKINSONISM
  申请人：Nuvamid SA

  公开号：EP4079311A1

  公开（公告）日：2022-10-26

  The invention relates to compounds of formula (I) and/or of formula (Ia) for the prevention and/or treatment of depression and/or anxiety related to a Parkinsonism such as an alpha-synucleinopathy as well as compositions and kit of parts comprising the same.

  本发明涉及用于预防和/或治疗与帕金森病（如α-突触核蛋白病）相关的抑郁和/或焦虑症的式(I)和/或式(Ia)化合物，以及包含这些化合物的组合物和试剂盒。