2-(3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione

• 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: 2-(3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione
• 英文别名: 2-{3-[4-(pyrimidin-2-yl)piperazin-1-yl]propyl}-2,3-dihydro-1H-isoindole-1,3-dione；2-[3-(4-pyrimidin-2-ylpiperazin-1-yl)propyl]isoindole-1,3-dione
• 化学式: C₁₉H₂₁N₅O₂
• 分子量: 351.408
• InChiKey: CTAKPOJQJJTDFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  69.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 3-(4-嘧啶-2-哌嗪)-1-丙胺
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085
• 作为产物：
  描述：

  1-(2-pyrimidyl)piperazine dihydrochloride 、 N-(3-溴丙基)苯二胺 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 20.0h， 以100%的产率得到2-(3-(4-(pyrimidin-2-yl)piperazin-1-yl)propyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Benzyl Phenylsemicarbazides: A Chemistry-Driven Approach Leading to G Protein-Biased Dopamine D₄ Receptor Agonists with High Subtype Selectivity

  摘要：

  Many subtype-selective dopamine receptor ligands developed for the D-2-D-4 family incorporate a 1-arylpiperazine-derived primary recognition motif, which is connected to a lipophilic moiety occupying an extended binding pocket (EBP) of the receptor via an aliphatic linker of variable lengths. The evaluation of a novel group of dopamine receptor ligands now showed that highly subtype-selective ligands [up to K-i(D-4.4) = 0.25 nM, D-2L/D-4.4 = 320, D-3/D-4.4 = 710 for APH199 (17)] can be obtained by choosing a relatively large and conformationally flexible 1-benzyl-1-phenylsemicarbazide substructure to fill the EBP. The novel chemotype APH199 (17) was found to act as a full agonist at the D-4 receptor showing significant bias toward G protein activation over beta-arrestin recruitment in comparison to quinpirole.

  DOI：

  10.1021/acs.jmedchem.9b01085

文献信息

• 2-Pyrimidinyl-l-piperazin-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
  申请人：Troponwerke GmbH & Co. KG

  公开号：EP0129128A2

  公开（公告）日：1984-12-27

  Die vorliegende Erfindung betrifft neue substituierte 2-Pyrimidinyt-l-piperazin.Denvate der allgemeinen Formel (I), Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel, insbesondere das zentrale Nervensystem beeinflussende Mittel.

  本发明涉及通式（I）的新取代的 2-嘧啶基-l-哌嗪变性物、其制备工艺和含有它们的药物，特别是影响中枢神经系统的药物。
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  申请人：——

  公开号：US4818756A

  公开（公告）日：1989-04-04
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  公开号：US4988809A

  公开（公告）日：1991-01-29
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  申请人：——

  公开号：US4937343A

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• US5187276A
  申请人：——

  公开号：US5187276A

  公开（公告）日：1993-02-16