2β-carboxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane | 306740-52-3

• 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: 2β-carboxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
• 英文别名: 3β-(3,4-dichlorophenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid；2β-carboxy-3β-(3,4-dichlorophenyl)tropane；(1R,2S,3S,5S)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid
• CAS: 306740-52-3
• 化学式: C₁₅H₁₇Cl₂NO₂
• 分子量: 314.211
• InChiKey: KAWFWFWGYBNWIW-PJQZNRQZSA-N

物化性质

• 沸点：
  448.6±45.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2β-carboxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane 在 三乙胺 、 N,N-二异丙基乙胺 、 肼 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 142.5h， 生成 2-(3-sec-butylimino-6-diethylamino-3H-xanthen-9-yl)-5-(5-{2-[3β-(3,4-dichlorophenyl)-8-methyl-8-aza-bicyclo[3.2.1]octane-2β-carbonyloxy]ethylcarbamoyl}pentylsulfamoyl)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：

  dicholoropane 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 24.0h， 以28%的产率得到2β-carboxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Intermediates for the synthesis of radiolabelled tropanes

  摘要：

  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。

  公开号：

  EP1238978A3

文献信息

• 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。
• Boat tropanes
  申请人：——

  公开号：US20020131931A1

  公开（公告）日：2002-09-19

  Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter over the serotonin transporter with a ratio of 10 or more. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.

  本发明公开了放射性药物复合物。一种托烷化合物通过 8 位上的 N 原子与一种能与锝或铼络合的螯合配体相连，从而产生一种中性标记的复合物，该复合物能选择性地与多巴胺转运体结合，而与血清素转运体的结合比例为 10 或更高。这些化合物既可以制备成单独的非对映异构体，也可以制备成非对映异构体的混合物。还公开了用于制备标记放射性药物化合物的放射性药物试剂盒。
• A Second-Generation ^99mTechnetium Single Photon Emission Computed Tomography Agent That Provides in Vivo Images of the Dopamine Transporter in Primate Brain
  作者：Peter C. Meltzer、Paul Blundell、Thomas Zona、Lihua Yang、Hong Huang、Ali A. Bonab、Eli Livni、Alan Fischman、Bertha K. Madras

  DOI：10.1021/jm0301484

  日期：2003.7.1

  The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for Parkinson's disease (Pd) and attention deficit hyperactivity disorder (ADHD). In ADHD, DAT density levels are elevated, while in Pd these levels are depleted. The depletion of DAT levels also corresponds with the loss of dopamine. We now describe the design, synthesis, biology, and SPECT imaging in nonhuman primates of second-generation (99m)technetium-based tropane ligands that bind potently and selectively to the DAT. We demonstrate that improved selectivity and biological stability allows sufficient agent to enter the brain and label the DAT in vivo to provide a quantitative measure of DAT density in nonhuman primates. We introduce FLUORATEC (N-[(2-((3'-N-propyl-(1"R)-3"alpha-(4-fluorophenyl)tropane-2"beta-1-propanoyl)(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato]technetium(V) oxide), a DAT imaging agent that has emerged from these studies and is now in phase 1 clinical trials in the U.S.
• Dopamine transporter imaging agents
  申请人：President and Fellows of Harvard College

  公开号：EP1051980B1

  公开（公告）日：2010-12-15
• US6548041B1
  申请人：——

  公开号：US6548041B1

  公开（公告）日：2003-04-15