(-)-2-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propylamino)-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanone | 1026084-33-2

• 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-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propylamino)-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanone
• CAS: 1026084-33-2
• 化学式: C₂₂H₂₉Cl₂N₅OS
• 分子量: 482.477
• InChiKey: NCNWKJNYDDJCJX-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  65.7
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (-)-2-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propylamino)-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanone 在 borane tetrahydrofuran 作用下， 以 四氢呋喃 为溶剂， 反应 36.0h， 生成 (-)-N⁶-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine
  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：

  普拉克索 、 2-chloro-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanone 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以44%的产率得到(-)-2-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)(propylamino)-1-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethanone
  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