2β-carboxy-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane | 53898-64-9

• 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-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
• 英文别名: 3β-[4-Fluorophenyl]tropan-2β-carboxylic Acid；2β-carboxy-3β-(4-fluorophenyl)tropane；Unii-6wjy4C4bcq；(1R,2S,3S,5S)-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid
• CAS: 53898-64-9
• 化学式: C₁₅H₁₈FNO₂
• 分子量: 263.312
• InChiKey: UAVJURKSCUOSRS-DGAVXFQQSA-N

物化性质

• 沸点：
  397.3±42.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 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：
  4

反应信息

• 作为反应物：
  描述：

  2β-carboxy-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.75h， 生成 3β-(p-fluorophenyl)-8-methyl-2β-propanoyl-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
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 水 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 反应 5.0h， 生成 2β-carboxy-3β-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies

  摘要：

  Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3 beta -aryl-2 beta-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [H-3]2 beta -carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00625-4

文献信息

• Synthesis and Characterization of Technetium-99m-Labeled Tropanes as Dopamine Transporter-Imaging Agents
  作者：Sanath K. Meegalla、Karl Plössl、Mei-Ping Kung、Sumalee Chumpradit、D. Andrew Stevenson、Steven A. Kushner、William T. McElgin、P. David Mozley、Hank F. Kung

  DOI：10.1021/jm960532j

  日期：1997.1.1

  striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating

  在开发新型Tc-99m标记的托烷衍生物作为多巴胺转运蛋白（再摄取位点）成像剂时，一系列含有中性和亲脂性的复合物，其中双-（氨基乙硫醇）作为[99mTc] TcO3 +中心核的中性复合部分。准备成功。据报道，Tc-99m标记的复合物13-16作为中枢神经系统（CNS）多巴胺转运蛋白成像剂的生物学评估。通过添加两个氨基乙硫醇单元的逐步反应，可以合成托烷衍生物。通过用Hg（OAc）2使4-甲氧基苄基保护基解封以获得三氟乙酸盐，从而获得最终的游离硫醇配体。除16种化合物外，所有Tc-99m复合物在多巴胺转运蛋白集中的纹状体区域均表现出良好的初始大脑摄取和选择性摄取。化合物之一，[2-[[2-[[[3-（4-氯苯基）-8-甲基-8-氮杂双环[3.2.1]辛-2-基]甲基]（2-巯基乙基）氨基] [etheth] amino] ethanethiolato-（3-）-N2，N2'，S2，S2'] oxo-
• METHODS FOR ARRANGING AND PACKING NUCLEIC ACIDS FOR UNUSUAL RESISTANCE TO NUCLEASES AND TARGETED DELIVERY FOR GENE THERAPY
  申请人：The Regents of the University of California

  公开号：US20150190525A1

  公开（公告）日：2015-07-09

  There are disclosed compositions and methods to render nucleic acids resistant to nuclease digestion while maintaining sequence selective hybridization competency. The approach relies on utilizing nucleic acids as the polar head group of a nucleic acid-polymer amphiphile in order to assemble well-defined, discrete micellar nanoparticles. Dense packing of nucleic acid in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation.

  本文披露了一种使核酸在维持序列选择性杂交能力的同时抵抗核酸酶消化的组合物和方法。该方法依赖于利用核酸作为核酸-聚合物两性分子的极性头基，以组装明确定义的离散胶束纳米粒子。在胶束包层中核酸的密集包装允许互补寡核苷酸的杂交，同时禁止酶降解。
• 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。
• Tropane compounds
  申请人：——

  公开号：US20030232819A1

  公开（公告）日：2003-12-18

  The present invention provides novel tropane compounds and methods for their use.

  本发明提供了新型的托品化合物及其使用方法。
• Aryl substituted heterocyclic compounds
  申请人：NEUROSEARCH A/S

  公开号：EP0604352A2

  公开（公告）日：1994-06-29

  The present invention discloses compounds of the formula any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein R, R3, and R4 each have the meanings set forth in the specification. The compounds possess valuable pharmaceutical properties as dopamine reuptake inhibitors.

  本发明公开了如下式的化合物 其任何混合物或其药学上可接受的盐； 其中 R、R3 和 R4 各自具有说明书中规定的含义。 这些化合物作为多巴胺再摄取抑制剂具有宝贵的药用特性。