2-(4-(isoquinolin-1-yl)piperazin-1-yl)-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylacetamide | 1202880-29-2

• 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-(4-(isoquinolin-1-yl)piperazin-1-yl)-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylacetamide
• 英文别名: 2-(4-isoquinolin-1-ylpiperazin-1-yl)-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylacetamide
• CAS: 1202880-29-2
• 化学式: C₂₉H₃₆N₄O₂
• 分子量: 472.63
• InChiKey: VLBLZXJEIHKWJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  48.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-(isoquinolin-1-yl)piperazin-1-yl)-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylacetamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以87%的产率得到N-(2-(4-(isoquinolin-1-yl)piperazin-1-yl)ethyl)-7-methoxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine
  参考文献：
  名称：

  Development of (S)-N⁶-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and Its Analogue as a D3 Receptor Preferring Agonist: Potent in Vivo Activity in Parkinson’s Disease Animal Models

  摘要：

  Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out, Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K-i). 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. SAR results identified compound (-)-24c (D301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.

  DOI：

  10.1021/jm901184n
• 作为产物：
  描述：

  2-chloro-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propyl-acetamide 、 1-哌嗪-1-异喹啉 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以87%的产率得到2-(4-(isoquinolin-1-yl)piperazin-1-yl)-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylacetamide
  参考文献：
  名称：

  Development of (S)-N⁶-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and Its Analogue as a D3 Receptor Preferring Agonist: Potent in Vivo Activity in Parkinson’s Disease Animal Models

  摘要：

  Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out, Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K-i). 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. SAR results identified compound (-)-24c (D301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.

  DOI：

  10.1021/jm901184n

文献信息

• Development of (<i>S</i>)-<i>N</i>⁶-(2-(4-(Isoquinolin-1-yl)piperazin-1-yl)ethyl)-<i>N</i>⁶-propyl-4,5,6,7-tetrahydrobenzo[<i>d</i>]-thiazole-2,6-diamine and Its Analogue as a D3 Receptor Preferring Agonist: Potent in Vivo Activity in Parkinson’s Disease Animal Models
  作者：Balaram Ghosh、Tamara Antonio、Juan Zhen、Prashant Kharkar、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm901184n

  日期：2010.2.11

  Here we report structure-activity relationship study of a novel hybrid series of compounds where structural alteration of aromatic hydrophobic moieties connected to the piperazine ring and bioisosteric replacement of the aromatic tetralin moieties were carried out, Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K-i). 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. SAR results identified compound (-)-24c (D301) as one of the lead molecules with preferential agonist activity for D3 receptor (EC50 (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC50): 223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity. The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA induced unilaterally lesioned rat model. Future studies will explore potential use of these compounds in the neuroprotective therapy for PD.