[18F]fluoroethyl-4-piperidyl acetate | 492446-38-5

• 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: [18F]fluoroethyl-4-piperidyl acetate
• 英文别名: N-[18F]fluoroethyl-4-piperidinyl acetate；N-(2-[18F]fluoroethyl)piperidin-4-yl acetate；N-(2-[18F]fluoroethyl)-4-piperidyl acetate；N-[18F]fluoroethylpiperidin-4-acetate；[1-(2-(18F)fluoranylethyl)piperidin-4-yl] acetate
• CAS: 492446-38-5
• 化学式: C₉H₁₆FNO₂
• 分子量: 188.232
• InChiKey: LGIBFTXNELWMLC-LMANFOLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [18F]fluoroethyl-4-piperidyl acetate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.08h， 生成 N-(2-[18F]fluoroethyl)-4-piperidinol
  参考文献：
  名称：

  N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A)

  摘要：

  N-[F-18]Fluoroethyl-4-piperidyl acetate ([F-18]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [F-18]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[F-18]fluoroethyl bromide ([F-18]FEtBr) at 130degreesC for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [F-18]FEtP4A was synthesized by reacting P4A with 2-[F-18]fluoroethyl iodide (([1)8F]FEtI) or 2-[F-18]fluoroethyl triflate ([F-18]FEtOTf in improved radiochemical yields, compared with [F-18]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [F-18]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of F-18 radioactivity was consistent with that of AchE in the brain: striatum > frontal cortex > cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [F-18]fluoroethyl-4-piperidinol ([F-18]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [F-18]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [F-18]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [C-11]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00177-9
• 作为产物：
  描述：

  哌啶-4-基乙酸酯 、 2-[18F]fluoroethyl triflate 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 [18F]fluoroethyl-4-piperidyl acetate
  参考文献：
  名称：

  How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf

  摘要：

  [18F]氟乙基溴 ([18F]FEtBr) 是合成 18F 标记化合物的有用合成前体。然而，[18F]FEtBr与胺、酚和酰胺官能团的反应活性低于[11C]CH3I，部分限制了其在[18F]氟乙基化化合物合成中的广泛应用。本研究的目的是提高 [18F]FEtBr 与各种亲核底物的反应性，用于含有胺、苯酚和酰胺部分的 PET 示踪剂。目前的策略包括（1）将NaI添加到[18F]FEtBr和底物的反应混合物中，其中[18F]FEtI可逆地形成并变得更具反应性； (2) 将[ 18F]FEtBr 转化为更具反应性的[ 18F]FEtOTf ，类似于将[ 11C]CH3I 转化为[ 11C]CH3OTf 。通过这些努力，与[18F]FEtBr的相应反应效率相比，[18F]FEtBr/NaI和[18F]FEtOTf对各种含有胺、酚和酰胺基团的底物的[18F]氟乙基化效率显着提高。版权所有 © 2003 约翰·威利父子有限公司

  DOI：

  10.1002/jlcr.703

文献信息

• How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf
  作者：Ming-Rong Zhang、Kenji Furutsuka、Yuichiro Yoshida、Kazutoshi Suzuki

  DOI：10.1002/jlcr.703

  日期：2003.5

  [18F]Fluoroethyl bromide ([18F]FEtBr) is a useful synthetic precursor to synthesize 18F-labeled compounds. However, the lower reactivity of [18F]FEtBr with amine, phenol and amide functional groups than that of [11C]CH3I partly limits its wide application in the synthesis of [18F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [18F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [18F]FEtBr and substrate, where [18F]FEtI is reversibly formed and becomes more reactive; (2) converting [18F]FEtBr into much more reactive [18F]FEtOTf, similar to conversion of [11C]CH3I into [11C]CH3OTf. By these efforts, the [18F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [18F]FEtBr/NaI and [18F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [18F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.

  [18F]氟乙基溴 ([18F]FEtBr) 是合成 18F 标记化合物的有用合成前体。然而，[18F]FEtBr与胺、酚和酰胺官能团的反应活性低于[11C]CH3I，部分限制了其在[18F]氟乙基化化合物合成中的广泛应用。本研究的目的是提高 [18F]FEtBr 与各种亲核底物的反应性，用于含有胺、苯酚和酰胺部分的 PET 示踪剂。目前的策略包括（1）将NaI添加到[18F]FEtBr和底物的反应混合物中，其中[18F]FEtI可逆地形成并变得更具反应性； (2) 将[ 18F]FEtBr 转化为更具反应性的[ 18F]FEtOTf ，类似于将[ 11C]CH3I 转化为[ 11C]CH3OTf 。通过这些努力，与[18F]FEtBr的相应反应效率相比，[18F]FEtBr/NaI和[18F]FEtOTf对各种含有胺、酚和酰胺基团的底物的[18F]氟乙基化效率显着提高。版权所有 © 2003 约翰·威利父子有限公司
• Efficient alkali iodide promoted 18F-fluoroethylations with 2-[18F]fluoroethyl tosylate and 1-bromo-2-[18F]fluoroethane
  作者：Andreas Bauman、Markus Piel、Ralf Schirrmacher、Frank Rösch

  DOI：10.1016/j.tetlet.2003.10.034

  日期：2003.12

  Radiochemical F-18-fluorination yields of several compounds using the secondary labelling precursors 2-[F-18]fluoroethyl tosylate ([(18)]FETos) and 1-bromo-2-[F-18]fluoroethane ([F-18]BFE) could be considerably enhanced by the addition of an alkali iodide. The radiochemical yield of [F-18]fluoroethyl choline for example could be doubled with [F-18]BFE and increased from 13% to approximate to80% with [F-18]FETos. By addition of alkali iodide to the precursor, the F-18-fluoroethylation yields of established radiopharmaceuticals, especially in the case of automated syntheses, could be significantly increased without major changes of the reaction conditions. (C) 2003 Elsevier Ltd. All rights reserved.
• Zhang, M. R.; Tsuchiyama, A.; Haradahira, T., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S883 - S885
  作者：Zhang, M. R.、Tsuchiyama, A.、Haradahira, T.、Yoshida, Y.、Irie, T.、Suzuki, K.

  DOI：——

  日期：——
• N-[18F]fluoroethyl-4-piperidyl acetate ([18F]FEtP4A)
  作者：Ming-Rong Zhang、Kenji Furutsuka、Jun Maeda、Tatsuya Kikuchi、Takayo Kida、Takashi Okauchi、Toshiaki Irie、Kazutoshi Suzuki

  DOI：10.1016/s0968-0896(03)00177-9

  日期：2003.6

  N-[F-18]Fluoroethyl-4-piperidyl acetate ([F-18]FEtP4A) was synthesized and evaluated as a PET tracer for imaging brain acetylcholinesterase (AchE) in vivo. [F-18]FEtP4A was previously prepared by reacting 4-piperidyl acetate (P4A) with 2-[F-18]fluoroethyl bromide ([F-18]FEtBr) at 130degreesC for 30 min in 37% radiochemical yield using an automated synthetic system. In this work, [F-18]FEtP4A was synthesized by reacting P4A with 2-[F-18]fluoroethyl iodide (([1)8F]FEtI) or 2-[F-18]fluoroethyl triflate ([F-18]FEtOTf in improved radiochemical yields, compared with [F-18]FEtBr under the corresponding condition. Ex vivo autoradiogram of rat brain and PET summation image of monkey brain after iv injection of [F-18]FEtP4A displayed a high radioactivity in the striatum, a region with the highest AchE activity in the brain. Moreover, the distribution pattern of F-18 radioactivity was consistent with that of AchE in the brain: striatum > frontal cortex > cerebellum. In the rat and monkey plasma, two radioactive metabolites were detected. However, their presence might not preclude the imaging studies for AchE in the brain, because they were too hydrophilic to pass the blood-brain barrier and to enter the brain. In the rat brain, only [F-18]fluoroethyl-4-piperidinol ([F-18]FEtP4OH) was detected at 30 min postinjection. The hydrolytic [F-18]FEtP4OH displayed a slow washout and a long retention in the monkey brain until the PET experiment (120 min). Although [F-18]FEtP4A is a potential PET tracer for imaging AchE in vivo, its lower hydrolytic rate and lower specificity for AchE than those of [C-11]MP4A may limit its usefulness for the quantitative measurement for AchE in the primate brain. (C) 2003 Elsevier Science Ltd. All rights reserved.