2β-carboxylic acid methoxymethylamide-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane | 306740-53-4

• 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-carboxylic acid methoxymethylamide-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
• 英文别名: 2β-methoxymethylcarbamoyl-3β-(4-fluorophenyl)tropane；(1R,2S,3S,5S)-3-(4-fluorophenyl)-N-methoxy-N,8-dimethyl-8-azabicyclo[3.2.1]octane-2-carboxamide
• CAS: 306740-53-4
• 化学式: C₁₇H₂₃FN₂O₂
• 分子量: 306.38
• InChiKey: CZGFBAOBZNKZBU-JJXSEGSLSA-N

物化性质

• 熔点：
  120.1-122.5 °C
• 沸点：
  384.2±52.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	2β-carboxy-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane	53898-64-9	C15H18FNO2	263.312
  甲基(1R,2S,3S,5S)-3-(4-氟苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-甲酸酯	2β-carbomethoxy-3β-(4-fluorophenyl)tropane	50370-56-4	C16H20FNO2	277.339

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3β-(p-fluorophenyl)-8-methyl-2β-propanoyl-8-azabicyclo<3.2.1>octane	——	C17H22FNO	275.366
  ——	2β-(1-propanoyl)-3β-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane	306740-56-7	C16H20FNO	261.339
  ——	N-[2-(3'-N'-propyl-(1''R)-3''β-(4-fluorophenyl)tropane-2''β-(1-propanoyl))((2-((triphenylmethyl)thio)ethyl)amino)acetyl]-S-(triphenyl)-2-aminoethanethiol	306740-58-9	C63H66FN3O2S2	980.366

反应信息

• 作为反应物：
  描述：

  2β-carboxylic acid methoxymethylamide-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane 在 1-氯乙基氯甲酸酯 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醚 、 乙腈 为溶剂， 反应 27.0h， 生成 N-[2-(3'-N'-propyl-(1''R)-3''β-(4-fluorophenyl)tropane-2''β-(1-propanoyl))((2-((triphenylmethyl)thio)ethyl)amino)acetyl]-S-(triphenyl)-2-aminoethanethiol
  参考文献：
  名称：

  A Second-Generation ^99mTechnetium Single Photon Emission Computed Tomography Agent That Provides in Vivo Images of the Dopamine Transporter in Primate Brain

  摘要：

  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.

  DOI：

  10.1021/jm0301484
• 作为产物：
  描述：

  甲基(1R,2S,3S,5S)-3-(4-氟苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-甲酸酯 在 吡啶 、 草酰氯 、 水 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.75h， 生成 2β-carboxylic acid methoxymethylamide-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  A Second-Generation ^99mTechnetium Single Photon Emission Computed Tomography Agent That Provides in Vivo Images of the Dopamine Transporter in Primate Brain

  摘要：

  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.

  DOI：

  10.1021/jm0301484

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。
• 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
• US7105678B2
  申请人：——

  公开号：US7105678B2

  公开（公告）日：2006-09-12