(S)-(-)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde | 956412-66-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-(-)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde
• 英文别名: (S)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde；(2S)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde
• CAS: 956412-66-1
• 化学式: C₁₄H₂₀N₂O₂
• 分子量: 248.325
• InChiKey: NNKMKNIPZHPUNI-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-(-)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde 在 正丁基锂 、 1-氯乙基氯甲酸酯 、 硫酸 、 水 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 1,2-二氯乙烷 为溶剂， 反应 26.17h， 生成 (S)-1-[2'-(methoxymethyl)piperazin-1'-yl]isoquinoline
  参考文献：
  名称：

  WO2008/115593

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-(4-苄基哌嗪-2-基)甲醇 在 乙酸酐 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.41h， 生成 (S)-(-)-4-benzyl-2-(methoxymethyl)piperazine-1-carbaldehyde
  参考文献：
  名称：

  WO2008/115593

  摘要：

  公开号：

文献信息

• Enantiomers of 2'-fluoralkyl-6-nitroquipazine as serotonin transporter positron emission tomography imaging agents and antidepressant therapeutics
  申请人：Gerdes M. John

  公开号：US20080058344A1

  公开（公告）日：2008-03-06

  Racemic mixtures and individual enantiomers of fluorine-18 or carbon-11 radio-labelled 2′-alkyl-6-nitroquipazine ligands are serotonin transporter (SERT) tracers for positron emission tomography (PET) imaging. The non-radioactive ligand forms possess therapeutic antidepressant in vitro and in vivo pharmacological binding profiles in rodent brain and cells expressing human serotonin transporter (hSERT). Twelve 2′-alkyl-6-nitroquipazine ligands potently bind in sub-nanomolar concentrations to the pre-synaptic SERT binding site where established antidepressant drugs bind and inhibit the re-uptake of the neurotransmitter serotonin (5-HT). In vivo tracer studies in rats as well as monkey PET scan trial have demonstrated the fluorine-18 and carbon-11 positron radionuclide labeled tracers perform as quantitative tracers of specific binding the SERT protein in live brain.

  2'-烷基-6-硝基奎普嗪配体的混合物和单一对映体，标记有氟-18或碳-11放射性同位素，是血清素转运体（SERT）正电子发射断层扫描（PET）成像的示踪剂。非放射性配体在啮齿动物大脑和表达人类血清素转运体（hSERT）的细胞中具有治疗性抗抑郁药物的体外和体内药理结合特性。12种2'-烷基-6-硝基奎普嗪配体在亚纳摩尔浓度下强烈结合于前突触SERT结合位点，这是已知抗抑郁药物结合并抑制神经递质血清素（5-HT）再摄取的位置。在大鼠体内示踪剂研究以及猴PET扫描试验中，氟-18和碳-11正电子放射性同位素标记的示踪剂表现为定量示踪剂，可在活体大脑中定位SERT蛋白的特异性结合。
• 1-[(2'-Substituted)-piperazin-1' -yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents
  申请人：Gerdes John M.

  公开号：US20080267870A1

  公开（公告）日：2008-10-30

  Racemic mixtures and enantiomerically pure forms of novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinolines are norepinephrine (NE) transporter (NET) inhibitor compounds. Compounds of the invention are considered therapeutic agents for central nervous system (CNS) diseases and disorders, without limitation, including neurodegeneration, anxiety, depression, attention deficit disorders, drug dependency, and post traumatic stress disorder. Examples of the chemical syntheses of the compounds of the invention are provided. The isoquinoline compounds of the invention competitively bind at NET at nanomolar concentrations. The isoquinoline agents of the invention bind selectively to NET over other competitive transporter targets and receptor binding sites, including those of serotonin and dopamine, amongst others. The chemical syntheses of the invention are suitable for labeling with radionuclide atoms. Radiolabeled forms of the novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinoline compounds are positron emission tomography and single photon emission tomography imaging tracers. Methods of in vivo imaging with the tracers within various subjects and tissues therein, including regions of the brain, are provided. Imaging methods with the tracers in combination other NET inhibitor agents are provided. The imaging methods within subjects allow quantitative detection of NET, determinations of NET distributions, and measures of tracer interactions at NET in the presence or absence of non-radioactive NET agents. The tracer imaging methods are suitable to locate, diagnose, identify, evaluate, detect or quantitate NET, or abnormalities of NET, or NE abnormalities; that are associated with various CNS diseases and disorders.

  本发明涉及新型的1-[(2'-取代)-哌嗪-1'-基]-异喹啉的混合物和对映纯形式，这些化合物是去甲肾上腺素转运体（NET）抑制剂化合物。本发明的化合物被认为是治疗中枢神经系统（CNS）疾病和障碍的治疗剂，包括但不限于神经退行性疾病、焦虑、抑郁、注意力缺陷障碍、药物依赖和创伤后应激障碍。本发明提供了化合物的化学合成的示例。本发明的异喹啉化合物在纳摩尔浓度下竞争性地结合于NET。本发明的异喹啉剂在选择性结合于NET而不是其他竞争性转运体靶点和受体结合位点，包括血清素和多巴胺等。本发明的化学合成适用于用放射性核素原子标记。放射性标记的新型1-[(2'-取代)-哌嗪-1'-基]-异喹啉化合物是正电子发射断层扫描和单光子发射断层扫描成像示踪剂。提供了在各种受试者和其中的组织，包括大脑区域内，与示踪剂的体内成像方法。提供了与其他NET抑制剂联合使用的示踪剂成像方法。受试者内的成像方法允许定量检测NET，确定NET分布，并测量在存在或不存在非放射性NET剂的情况下示踪剂与NET的相互作用。示踪剂成像方法适用于定位、诊断、鉴定、评估、检测或定量NET或与各种CNS疾病和障碍相关的NE异常或NET异常。
• 1-[(2′-substituted)-piperazin-1′ -yl]-isoquinolines as norepinephrine transporter inhibitor therapeutics and positron emission tomography imaging agents
  申请人：University of Montana

  公开号：US07887784B2

  公开（公告）日：2011-02-15

  Racemic mixtures and enantiomerically pure forms of novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinolines are norepinephrine (NE) transporter (NET) inhibitor compounds. Compounds of the invention are considered therapeutic agents for central nervous system (CNS) diseases and disorders, without limitation, including neurodegeneration, anxiety, depression, attention deficit disorders, drug dependency, and post traumatic stress disorder. Examples of the chemical syntheses of the compounds of the invention are provided. The isoquinoline compounds of the invention competitively bind at NET at nanomolar concentrations. The isoquinoline agents of the invention bind selectively to NET over other competitive transporter targets and receptor binding sites, including those of serotonin and dopamine, amongst others. The chemical syntheses of the invention are suitable for labeling with radionuclide atoms. Radiolabeled forms of the novel 1-[(2′-substituted)-piperazin-1′-yl]-isoquinoline compounds are positron emission tomography and single photon emission tomography imaging tracers. Methods of in vivo imaging with the tracers within various subjects and tissues therein, including regions of the brain, are provided. Imaging methods with the tracers in combination other NET inhibitor agents are provided. The imaging methods within subjects allow quantitative detection of NET, determinations of NET distributions, and measures of tracer interactions at NET in the presence or absence of non-radioactive NET agents. The tracer imaging methods are suitable to locate, diagnose, identify, evaluate, detect or quantitate NET, or abnormalities of NET, or NE abnormalities; that are associated with various CNS diseases and disorders.

  该发明涉及新型1-[(2'-取代)-哌嗪-1'-基]-异喹啉的外消旋混合物和对映纯形式，它们是去甲肾上腺素（NE）转运体（NET）抑制剂化合物。该发明的化合物被认为是治疗中枢神经系统（CNS）疾病和障碍的治疗剂，包括但不限于神经退行性疾病、焦虑、抑郁、注意力缺陷障碍、药物依赖和创伤后应激障碍等。提供了该发明化合物的化学合成实例。该发明的异喹啉化合物在纳摩尔浓度下竞争性地结合于NET。该发明的异喹啉剂在选择性结合于NET而不是其他竞争性转运体靶点和受体结合位点，包括血清素和多巴胺等。该发明的化学合成适用于用放射性核素原子标记。新型1-[(2'-取代)-哌嗪-1'-基]-异喹啉化合物的放射性标记形式是正电子发射断层扫描和单光子发射断层扫描成像示踪剂。提供了使用这些示踪剂在各种受试者和其中的组织，包括大脑区域内进行体内成像的方法。提供了使用这些示踪剂与其他NET抑制剂一起进行成像的方法。在受试者中使用示踪剂的成像方法允许定量检测NET、确定NET分布以及测量在存在或不存在非放射性NET剂的情况下示踪剂与NET的相互作用。示踪剂成像方法适用于定位、诊断、鉴定、评估、检测或量化与各种CNS疾病和障碍相关的NET或NET异常。
• Enantiomers of 2'-Fluoralkyl-6-nitroquipazine as Serotonin Transporter Positron Emission Tomography Imaging Agents and Antidepressant Therapeutics
  申请人：Gerdes John M.

  公开号：US20110009419A1

  公开（公告）日：2011-01-13

  Racemic mixtures and individual enantiomers of fluorine-18 or carbon-11 radiolabelled 2′-alkyl-6-nitroquipazine ligands are serotonin transporter (SERT) tracers for positron emission tomography (PET) imaging. The non-radioactive ligand forms possess therapeutic antidepressant in vitro and in vivo pharmacological binding profiles in rodent brain and cells expressing human serotonin transporter (hSERT). Twelve 2′-alkyl-6-nitroquipazine ligands potently bind in sub-nanomolar concentrations to the pre-synaptic SERT binding site where established antidepressant drugs bind and inhibit the re-uptake of the neurotransmitter serotonin (5-HT). In vivo tracer studies in rats as well as monkey PET scan trial have demonstrated the fluorine-18 and carbon-11 positron radionuclide labeled tracers perform as quantitative tracers of specific binding the SERT protein in live brain.

  氟-18或碳-11放射标记的2'-烷基-6-硝基喹嗪配体的外消旋混合物和单体对于正电子发射断层扫描（PET）成像是血清素转运体（SERT）示踪剂。非放射性配体形式在啮齿动物大脑和表达人类血清素转运体（hSERT）的细胞中具有治疗性抗抑郁药物的体外和体内药理结合特征。十二种2'-烷基-6-硝基喹嗪配体以亚纳摩尔浓度强烈结合于前突触SERT结合位点，已知抗抑郁药物在此处结合并抑制神经递质血清素（5-HT）的再摄取。在大鼠体内示踪剂研究以及猴PET扫描试验中，氟-18和碳-11正电子放射性标记的示踪剂表现为定量示踪剂，可在活体大脑中特异性结合SERT蛋白。
• WO2007/127262
  申请人：——

  公开号：——

  公开（公告）日：——