tert-Butyl (3R,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-Butyl (3R,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate
• 英文别名: tert-butyl (3R,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate
• 化学式: C₁₁H₂₁FN₂O₂
• 分子量: 232.298
• InChiKey: PWWDRFMQLZQJAY-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-Butyl (3R,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 2-甲基-2-丁醇 、 乙酸乙酯 为溶剂， 反应 48.75h， 生成
  参考文献：
  名称：

  Synthesis and in vitro characterization of trans- and cis-[18F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-d-aspartate receptor

  摘要：

  Diastereoisomeric compounds [F-18]cis- and [F-18]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD(7.4) values as well as B-max/K-d ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.011
• 作为产物：
  描述：

  3-氟-4-亚甲基哌啶-1-羧酸叔丁酯 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 氯化铵 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、120.0 kPa 条件下， 反应 29.25h， 生成 tert-Butyl (3R,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and in vitro characterization of trans- and cis-[18F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-d-aspartate receptor

  摘要：

  Diastereoisomeric compounds [F-18]cis- and [F-18]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD(7.4) values as well as B-max/K-d ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.04.011

文献信息

• Radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines and its application to new radiotracers for NR2B NMDA receptor visualization
  作者：Radouane Koudih、Gwénaëlle Gilbert、Martine Dhilly、Ahmed Abbas、Louisa Barré、Danièle Debruyne、Franck Sobrio

  DOI：10.1039/c2ob26378e

  日期：——

  In order to develop a novel and useful building block for the development of radiotracers for positron emission tomography (PET), we studied the radiolabelling of 1,4-disubstituted 3-[18F]fluoropiperidines. Indeed, 3-fluoropiperidine became a useful building block in medicinal chemistry for the pharmacomodulation of piperidine-containing compounds. The radiofluorination was studied on substituted piperidines with electron-donating and electron-withdrawing N-substituents. In the instance of electron-donating N-substituents such as benzyl or butyl, configuration retention and satisfactory fluoride-18 incorporation yields up to 80% were observed. In the case of electron-withdrawing N-substituents leading to carbamate or amide functions, the incorporation yields depend on the 4-susbtitutent (2 to 63%). The radiolabelling of this building block was applied to the automated radiosynthesis of NR2B NMDA receptor antagonists and effected by a commercially available radiochemistry module. The in vivo evaluation of three radiotracers demonstrated minimal brain uptakes incompatible with the imaging of NR2B NMDA receptors in the living brain. Nevertheless, moderate radiometabolism was observed and, in particular, no radiodefluorination was observed which demonstrates the stability of the 3-position of the fluorine-18 atom. In conclusion, the 1,4-disubstituted 3-[18F]fluoropiperidine moiety could be of value in the development of other radiotracers for PET even if the evaluation of the NR2B NMDA receptor antagonists failed to demonstrate satisfactory properties for PET imaging of this receptor.

  为了开发用于正电子发射断层扫描（PET）示踪剂的新颖且有用的构建模块，我们研究了1,4-二取代的3-[18F]氟哌啶的放射性标记。实际上，3-氟哌啶已成为药物化学中含哌啶化合物的药效调控的有用构建模块。我们在具有供电子和吸电子N-取代基的取代哌啶上研究了放射性氟化。对于具有供电子N-取代基（如苄基或丁基）的情况，观察到了构型保持和令人满意的氟-18掺入产率，高达80％。在导致形成氨基甲酸酯或酰胺功能的吸电子N-取代基的情况下，掺入产率取决于4-取代基（2至63％）。该构建模块的放射性标记被应用于NR2B NMDA受体拮抗剂的自动放射合成，并通过商用的放射化学模块实现。对三种放射性示踪剂的体内评估显示，其脑摄取量极低，与在活脑中成像NR2B NMDA受体不兼容。然而，观察到了中等程度的放射性代谢，特别是未观察到放射性去氟化，这表明氟-18原子的3位点的稳定性。总之，1,4-二取代的3-[18F]氟哌啶部分可能对开发其他PET示踪剂有价值，即使NR2B NMDA受体拮抗剂的评估未能显示出适用于该受体PET成像的令人满意的特性。
• Synthesis and in vitro characterization of trans- and cis-[18F]-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoropiperidine-1-carboxylates as new potential PET radiotracer candidates for the NR2B subtype N-methyl-d-aspartate receptor
  作者：Radouane Koudih、Gwénaëlle Gilbert、Martine Dhilly、Ahmed Abbas、Louisa Barré、Danièle Debruyne、Franck Sobrio

  DOI：10.1016/j.ejmech.2012.04.011

  日期：2012.7

  Diastereoisomeric compounds [F-18]cis- and [F-18]trans-4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]-3-fluoro-piperidine-1-carboxylates were successfully synthesized as new subtype-selective PET radiotracers for imaging the NR2B subunit containing NMDA receptors. Rat brain section autoradiographies demonstrated a high specific binding in NR2B/NMDA receptor rich regions for both radioligands. The measured logD(7.4) values as well as B-max/K-d ratios indicated that both radiotracers possess the adequate properties required for PET radiotracers. (C) 2012 Elsevier Masson SAS. All rights reserved.