N⁶-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N⁶-(prop-2-ynyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine | 1026084-04-7

• 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: N⁶-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N⁶-(prop-2-ynyl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine
• 英文别名: 6-N-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]-6-N-prop-2-ynyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
• CAS: 1026084-04-7
• 化学式: C₂₂H₂₇Cl₂N₅S
• 分子量: 464.462
• InChiKey: AWFHSDHVMOYPMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  氰胺 、 4-((2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)(prop-2-ynyl)amino)cyclohexanone 在 四氢吡咯 、 对甲苯磺酸 、 sulfur 作用下， 以 苯 、 甲醇 为溶剂， 反应 13.83h， 以43%的产率得到N⁶-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)-N⁶-(prop-2-ynyl)-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

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.