5-fluoro-6-nitro-2-(piperazin-1-yl)quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-fluoro-6-nitro-2-(piperazin-1-yl)quinoline
• 英文别名: 5-fluoro-6-nitroquipazine；5-Fluoro-6-nitro-2-piperazinylquinoline；2-(Piperazin-1-yl)-5-fluoro-6-nitroquinoline；5-fluoro-6-nitro-2-piperazin-1-ylquinoline
• 化学式: C₁₃H₁₃FN₄O₂
• 分子量: 276.27
• InChiKey: FWINNVJMLWHYQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-bromo-6-nitro-2-(N-tert-butyloxycarbonylpiperazin-1-yl)quinoline 在 K[18/19F]F 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 三氟乙酸 作用下， 以 二甲基亚砜 、 二氯甲烷 为溶剂， 反应 0.11h， 生成 5-bromo-6-nitro-2-(piperazin-1-yl)quinoline 、 5-fluoro-6-nitro-2-(piperazin-1-yl)quinoline 、
  参考文献：
  名称：

  Synthesis of a fluorine-18-labelled derivative of 6-nitroquipazine, as a radioligand for the In vivo serotonin transporter imaging with PET

  摘要：

  Considerable efforts have been engaged in the design, synthesis and pharmacological characterization of radioligands for imaging the serotonin transporter, based on its implication in several neuropsychiatric diseases, Such as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series, the fluoro derivative has been designed for positron emission tomography (PET). The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference compound have been synthesized. 5-[F-18]Fluoro-6-nitroquipazine has been radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life) by nucleophilic aromatic substitution from the corresponding N-Boc protected 5-bromo- and 5-chloro-precursors using K[F-18]F-K-222 complex in DMSO by conventional heating (145degreesC, 2 min) or microwave activation (50 W, 30-45 s), followed by removal of the protective group with TFA. Typically, 15-25 mCi (5.5-9.2 GBq) of 5-[F-18]fluoro-6-nitroquipazine (1-2 Ci/mumol or 37-72 GBq/mumol) could be obtained in 70-80 min starting from a 550-650 mCi (20.3-24.0 GBq) aliquot of a cyclotron [F-18]F- production batch (2.7-3.8% non decay-corrected yield based on the starting [F-18]fluoride). Ex vivo studies (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5-[(18)]fluoro-6-nitroquipazine ([F-18]-1d) readily crossed the blood brain barrier and accumulated in the regions rich in 5-HT transporter (frontal-and posterial cortex, striata). However, the low accumulation of the tracer in the thalamus (rat and monkey) as well as the comparable displacement of the tracer observed with both citalopram, a reference 5-HT re-uptake inhibitor and maprotiline, a norepinephrine re-uptake inhibitor (rat), indicate that 5-[F-18]fluoro-6-nitroquipazine ([F-18]-1d) does not have the suggested potential for PFT imaging of the serotin transporter (SERT). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00098-6

文献信息

• US5372813A
  申请人：——

  公开号：US5372813A

  公开（公告）日：1994-12-13
• Synthesis of a fluorine-18-labelled derivative of 6-nitroquipazine, as a radioligand for the In vivo serotonin transporter imaging with PET
  作者：Mylène Karramkam、Frédéric Dollé、Héric Valette、Laurent Besret、Yann Bramoullé、Françoise Hinnen、Françoise Vaufrey、Carine Franklin、Sébastien Bourg、Christine Coulon、Michèle Ottaviani、Marcel Delaforge、Christian Loc'h、Michel Bottlaender、Christian Crouzel

  DOI：10.1016/s0968-0896(02)00098-6

  日期：2002.8

  Considerable efforts have been engaged in the design, synthesis and pharmacological characterization of radioligands for imaging the serotonin transporter, based on its implication in several neuropsychiatric diseases, Such as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series, the fluoro derivative has been designed for positron emission tomography (PET). The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference compound have been synthesized. 5-[F-18]Fluoro-6-nitroquipazine has been radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life) by nucleophilic aromatic substitution from the corresponding N-Boc protected 5-bromo- and 5-chloro-precursors using K[F-18]F-K-222 complex in DMSO by conventional heating (145degreesC, 2 min) or microwave activation (50 W, 30-45 s), followed by removal of the protective group with TFA. Typically, 15-25 mCi (5.5-9.2 GBq) of 5-[F-18]fluoro-6-nitroquipazine (1-2 Ci/mumol or 37-72 GBq/mumol) could be obtained in 70-80 min starting from a 550-650 mCi (20.3-24.0 GBq) aliquot of a cyclotron [F-18]F- production batch (2.7-3.8% non decay-corrected yield based on the starting [F-18]fluoride). Ex vivo studies (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5-[(18)]fluoro-6-nitroquipazine ([F-18]-1d) readily crossed the blood brain barrier and accumulated in the regions rich in 5-HT transporter (frontal-and posterial cortex, striata). However, the low accumulation of the tracer in the thalamus (rat and monkey) as well as the comparable displacement of the tracer observed with both citalopram, a reference 5-HT re-uptake inhibitor and maprotiline, a norepinephrine re-uptake inhibitor (rat), indicate that 5-[F-18]fluoro-6-nitroquipazine ([F-18]-1d) does not have the suggested potential for PFT imaging of the serotin transporter (SERT). (C) 2002 Elsevier Science Ltd. All rights reserved.