N-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N-(prop-2-ynyl)-1,4-dioxaspiro[4.5]decan-8-amine | 1026083-88-4

• 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: N-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N-(prop-2-ynyl)-1,4-dioxaspiro[4.5]decan-8-amine
• CAS: 1026083-88-4
• 化学式: C₂₃H₃₁Cl₂N₃O₂
• 分子量: 452.424
• InChiKey: PICAPHRXSFOUKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  28.18
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N-(prop-2-ynyl)-1,4-dioxaspiro[4.5]decan-8-amine 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 以73%的产率得到4-((2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)(prop-2-ynyl)amino)cyclohexanone
  参考文献：
  名称：

  Bioisosteric Heterocyclic Versions of 7-{[2-(4-Phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol: Identification of Highly Potent and Selective Agonists for Dopamine D3 Receptor with Potent in Vivo Activity

  摘要：

  In the current report, we extend the SAR study on our hybrid structure 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol further to include heterocyclic bioisosteric analogues. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K). Functional activity of selected compounds in stimulating GTP gamma S binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. The highest binding affinity and selectivity for D3 receptors were exhibited by (-)-34 (K-i = 0.92 nM and D2/D3 = 253). In the functional GTP gamma S binding assay, (-)-34 exhibited full agonist activity with picomolar affinity for D3 receptor with high selectivity (EC50 = 0.08 nM and D2/D3 = 248). In the in vivo rotational study, (-)-34 exhibited potent rotational activity in 6-OH-DA unilaterally lesioned rats with long duration of action, which indicates its potential application in neuroprotective treatment of Parkinson's disease.

  DOI：

  10.1021/jm701524h
• 作为产物：
  描述：

  N-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-1,4-dioxaspiro[4.5]decan-8-amine 、 3-溴丙炔 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 、 甲苯 为溶剂， 反应 3.5h， 以39%的产率得到N-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N-(prop-2-ynyl)-1,4-dioxaspiro[4.5]decan-8-amine
  参考文献：
  名称：

  Bioisosteric Heterocyclic Versions of 7-{[2-(4-Phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol: Identification of Highly Potent and Selective Agonists for Dopamine D3 Receptor with Potent in Vivo Activity

  摘要：

  In the current report, we extend the SAR study on our hybrid structure 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol further to include heterocyclic bioisosteric analogues. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K). Functional activity of selected compounds in stimulating GTP gamma S binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. The highest binding affinity and selectivity for D3 receptors were exhibited by (-)-34 (K-i = 0.92 nM and D2/D3 = 253). In the functional GTP gamma S binding assay, (-)-34 exhibited full agonist activity with picomolar affinity for D3 receptor with high selectivity (EC50 = 0.08 nM and D2/D3 = 248). In the in vivo rotational study, (-)-34 exhibited potent rotational activity in 6-OH-DA unilaterally lesioned rats with long duration of action, which indicates its potential application in neuroprotective treatment of Parkinson's disease.

  DOI：

  10.1021/jm701524h