5-chloro-2-(piperazin-1-yl)quinoline | 124782-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-chloro-2-(piperazin-1-yl)quinoline
• 英文别名: 5-chloroquipazine；5-chloro-quipazine；5-chloro-2-piperazin-1-yl-quinoline；5-chloro-2-piperazin-1-ylquinoline
• CAS: 124782-91-8
• 化学式: C₁₃H₁₄ClN₃
• 分子量: 247.727
• InChiKey: JXMXQYPMWLBYGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 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：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-2-(piperazin-1-yl)quinoline 在 硫酸 、 硝酸 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 5-chloro-6-nitro-2-(N-tert-butyloxycarbonylpiperazin-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
• 作为产物：
  描述：

  5-氨基喹啉 在 盐酸 、 过氧乙酸 、 硫酸 、 sodium nitrite 、 三氯氧磷 作用下， 以 四氢呋喃 、 氯仿 、 水 为溶剂， 反应 7.17h， 生成 5-chloro-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

• Substituted piperazine derivatives, the preparation thereofand their use as medicaments
  申请人：——

  公开号：US20030166637A1

  公开（公告）日：2003-09-04

  The present invention relates to substituted piperazine derivatives of general formula 1 , (I wherein R a , R b , R c , R f , R g , X, m and n are defined as in claim 1, the isomers and salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.

  本发明涉及一般式1的取代哌嗪衍生物（I），其中Ra、Rb、Rc、Rf、Rg、X、m和n的定义如权利要求书中所述，其异构体和盐，特别是其生理上可接受的盐，这些盐是微粒体甘油三酯转移蛋白（MTP）的有价值的抑制剂，含有这些化合物的药物以及它们的使用，以及其制备。
• Substituted piperazine derivatives, the preparation thereof and their use as medicaments
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US06821967B2

  公开（公告）日：2004-11-23

  The present invention relates to substituted piperazine derivatives of general formula wherein Ra, Rb, Rc, Rf, Rg, X, m and n are defined as in claim 1, the isomers and salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.

  本发明涉及通式如下的取代哌嗪衍生物： 其中Ra、Rb、Rc、Rf、Rg、X、m和n如权利要求1所定义，其异构体和盐，特别是生理上可接受的盐，是微粒体甘油三酯转移蛋白（MTP）有价值的抑制剂，含有这些化合物的药物以及它们的用途，以及它们的制备。
• Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors
  作者：Małgorzata Jarończyk、Karol Wołosewicz、Mari Gabrielsen、Gabriel Nowak、Irina Kufareva、Aleksander P. Mazurek、Aina W. Ravna、Ruben Abagyan、Andrzej J. Bojarski、Ingebrigt Sylte、Zdzisław Chilmonczyk

  DOI：10.1016/j.ejmech.2012.01.012

  日期：2012.3

  It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquilex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro- and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. (C) 2012 Elsevier Masson SAS. All rights reserved.
• US6821967B2
  申请人：——

  公开号：US6821967B2

  公开（公告）日：2004-11-23
• 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.