[2-(4-phenylpiperazin-1-yl)ethyl]propyl(4,5,6,7-tetrahydrobenzo[d]isoxazol-5-yl)amine | 874459-30-0

• 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-(4-phenylpiperazin-1-yl)ethyl]propyl(4,5,6,7-tetrahydrobenzo[d]isoxazol-5-yl)amine
• 英文别名: N-[2-(4-phenylpiperazin-1-yl)ethyl]-N-propyl-4,5,6,7-tetrahydro-1,2-benzoxazol-5-amine
• CAS: 874459-30-0
• 化学式: C₂₂H₃₂N₄O
• 分子量: 368.522
• InChiKey: SYVXHALPVYBOLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  35.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-hydroxymethylene-4-{[2-(4-phenylpiperazin-1-yl)ethyl]propylamino}cyclohexanone 在 盐酸羟胺 、 溶剂黄146 作用下， 反应 1.0h， 以80%的产率得到[2-(4-phenylpiperazin-1-yl)ethyl]propyl(4,5,6,7-tetrahydrobenzo[d]isoxazol-5-yl)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

文献信息

• 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
  作者：Swati Biswas、Stuart Hazeldine、Balaram Ghosh、Ingrid Parrington、Eldo Kuzhikandathil、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm701524h

  日期：2008.5.1

  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.