(R)-1-benzyl-3-((tetrahydro-2H-pyran-2-yloxy)methyl)piperazine-2,5-dione | 1060720-31-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-1-benzyl-3-((tetrahydro-2H-pyran-2-yloxy)methyl)piperazine-2,5-dione
• 英文别名: (3R)-1-benzyl-3-(oxan-2-yloxymethyl)piperazine-2,5-dione
• CAS: 1060720-31-1
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: SMMCYVSKPXWKEP-IURRXHLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-benzyl-3-((tetrahydro-2H-pyran-2-yloxy)methyl)piperazine-2,5-dione 在 lithium aluminium tetrahydride 、 sodium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以99%的产率得到(S)-1-benzyl-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]piperazine
  参考文献：
  名称：

  WO2008/115593

  摘要：

  公开号：
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 、 (R)-3-(hydroxymethyl)-1-(phenylmethyl)-2,5-piperazinedione 在 对甲苯磺酸 、 水 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以93%的产率得到(R)-1-benzyl-3-((tetrahydro-2H-pyran-2-yloxy)methyl)piperazine-2,5-dione
  参考文献：
  名称：

  WO2008/115593

  摘要：

  公开号：

文献信息

• 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。
• 1-[(2'-SUBSTITUTED)-PIPERAZIN-1'-YL]-ISOQUINOLINES AS NOREPINEPHRINE TRANSPORTER INHIBITOR THERAPEUTICS AND POSITRON EMISSION TOMOGRAPHY IMAGING AGENTS
  申请人：The University Of Montana

  公开号：EP2139481B1

  公开（公告）日：2013-08-21
• US7887784B2
  申请人：——

  公开号：US7887784B2

  公开（公告）日：2011-02-15
• [EN] 1-[(2'-SUBSTITUTED)-PIPERAZIN-1'-YL]-ISOQUINOLINES AS NOREPINEPHRINE TRANSPORTER INHIBITOR THERAPEUTICS AND POSITRON EMISSION TOMOGRAPHY IMAGING AGENTS<br/>[FR] 1-[(2'-SUBSTITUÉ)-PIPÉRAZIN-1'-YL]-ISOQUINOLÉINES EN TANT QU'AGENTS THÉRAPEUTIQUES INHIBITEURS DE TRANSPORTEUR DE NORÉPINÉPHRINE ET AGENTS D'IMAGERIE DE TOMOGRAPHIE PAR ÉMISSION DE POSITONS
  申请人：UNIV MONTANA

  公开号：WO2008115593A1

  公开（公告）日：2008-09-25

  [EN] 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 comoundss 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.
  [FR] L'invention concerne des mélanges racémiques et des formes énantiomériquement pures de 1-[(2'-substitué)-pipérazin-1'-yl]-isoquinoléines novatrices en tant que composés inhibiteurs de transporteur de norépinephrine (NET) (NE). Les composés de l'invention sont considérés comme des agents thérapeutiques pour des maladies et troubles du système nerveux central (SNC), sans s'y limiter, comprenant, une neurodégénérescence, l'anxiété, la dépression, les troubles du déficit de l'attention, la toxicomanie et un trouble de stress post-traumatique. Des exemples des synthèses chimiques des composés de l'invention sont fournis. Les composés isoquinoléine de l'invention se lient de manière compétitive au NET à des concentrations nanomolaires. Les agents isoquinoléine de l'invention se lient sélectivement au NET par rapport à d'autres sites de transporteur compétitifs et d'autres sites de liaison de récepteur, comprenant ceux de la sérotonine et de la dopamine, entre autres. Les synthèses chimiques de l'invention sont appropriées pour le marquage avec des atomes de radionucléide. Des formes radiomarquées des composés 1-[(2'-substitué)-pipérazin-1'-yl]-isoquinoléine novateurs sont des traceurs d'imagerie de tomographie par émission de positons et de gammatomographie. Des procédés d'imagerie in vivo avec les traceurs au sein de divers sujets et tissus à l'intérieur, comprenant des régions du cerveau, sont proposés. Des procédés d'imagerie avec les traceurs en combinaison avec d'autres agents inhibiteurs de NET sont proposés. Les procédés d'imagerie au sein d'un sujet permettent la détection quantitative de NET, des déterminations de distribution de NET, et mesurent des interactions de traceurs au NET en présence ou en l'absence d'agents NET non radioactifs. Les procédés d'imagerie de traceur sont appropriés pour localiser, diagnostiquer, identifier, évaluer, détecter ou quantifier un NET, ou des anomalies de NET ou des anomalies de NE; qui sont associés à diverses maladies et troubles du SNC.