4-(3,4-dimethoxyphenethylamino)butanenitrile | 1021131-24-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3,4-dimethoxyphenethylamino)butanenitrile
• 英文别名: 4-[2-(3,4-Dimethoxyphenyl)ethylamino]butanenitrile
• CAS: 1021131-24-7
• 化学式: C₁₄H₂₀N₂O₂
• mdl: MFCD11151020
• 分子量: 248.325
• InChiKey: REZPXEWWROXICM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3,4-dimethoxyphenethylamino)butanenitrile 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and in vitro evaluation of tetrahydroisoquinolinyl benzamides as ligands for σ receptors

  摘要：

  5-Bromo-N-[4-(6,7-diinethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide (1) is one of the most potent and selective sigma(2) receptor ligands reported to date. Previous structure-activity relationship studies of such tetrahydroisoquinolinyl benzamides have focused on the linker that connects the ring systems and the effects of benzamide ring substituents. The present study explores the effects of fusing methylene-, ethylene-, and propylenedioxy rings onto the tetrahydroisoquinoline in place of the two methoxy groups. These modifications decreased sigma(2) affinity by 8- to 12-fold, with no major differences noted with ring size. By contrast, the methylenedioxy analog showed a 10-fold greater sigma(1) affinity than 1, and progressively lower sigma(1) affinities were then noted with increasing ring size. We also opened the tetrahydroisoquinoline ring of 1 to study the effects of greater conformational fluidity on a receptor binding. The sigma(2) affinity of the open-ring compound decreased by 1700-fold, while a, affinity was not changed. Thus, a constrained tetrahydroisoquinoline ring system is key to the exceptional sigma(2) receptor binding affinity and selectivity of this active series. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.005
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 、 4-溴丁腈 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以93%的产率得到4-(3,4-dimethoxyphenethylamino)butanenitrile
  参考文献：
  名称：

  Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors

  摘要：

  5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide (1) is one of the most potent and selective sigma(2) receptor ligands reported to date. A series of new analogs, where the amine ring fused to the aromatic ring was varied in size (5-7) and the location of the nitrogen in this ring was modified, has been synthesized and assessed for their sigma(1)/sigma(2) binding affinity and selectivity. The binding affinity of an open-chained variant of 1 was also evaluated. Only the five-membered ring congener of 1 displayed a higher sigma(1)/sigma(2) selectivity, derived from a higher sigma(2) affinity and a lower sigma(1) affinity. Positioning the nitrogen adjacent to the aromatic ring in the five-membered and six-membered ring congeners dramatically decreased affinity for both subtypes. Thus, location of the nitrogen within a constrained ring is confirmed to be key to the exceptional sigma(2) receptor binding affinity and selectivity for this active series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.006

文献信息

• Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors
  作者：Kuo-Hsien Fan、John R. Lever、Susan Z. Lever

  DOI：10.1016/j.bmc.2011.02.006

  日期：2011.3

  5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide (1) is one of the most potent and selective sigma(2) receptor ligands reported to date. A series of new analogs, where the amine ring fused to the aromatic ring was varied in size (5-7) and the location of the nitrogen in this ring was modified, has been synthesized and assessed for their sigma(1)/sigma(2) binding affinity and selectivity. The binding affinity of an open-chained variant of 1 was also evaluated. Only the five-membered ring congener of 1 displayed a higher sigma(1)/sigma(2) selectivity, derived from a higher sigma(2) affinity and a lower sigma(1) affinity. Positioning the nitrogen adjacent to the aromatic ring in the five-membered and six-membered ring congeners dramatically decreased affinity for both subtypes. Thus, location of the nitrogen within a constrained ring is confirmed to be key to the exceptional sigma(2) receptor binding affinity and selectivity for this active series. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and in vitro evaluation of tetrahydroisoquinolinyl benzamides as ligands for σ receptors
  作者：Rong Xu、John R. Lever、Susan Z. Lever

  DOI：10.1016/j.bmcl.2007.02.005

  日期：2007.5

  5-Bromo-N-[4-(6,7-diinethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide (1) is one of the most potent and selective sigma(2) receptor ligands reported to date. Previous structure-activity relationship studies of such tetrahydroisoquinolinyl benzamides have focused on the linker that connects the ring systems and the effects of benzamide ring substituents. The present study explores the effects of fusing methylene-, ethylene-, and propylenedioxy rings onto the tetrahydroisoquinoline in place of the two methoxy groups. These modifications decreased sigma(2) affinity by 8- to 12-fold, with no major differences noted with ring size. By contrast, the methylenedioxy analog showed a 10-fold greater sigma(1) affinity than 1, and progressively lower sigma(1) affinities were then noted with increasing ring size. We also opened the tetrahydroisoquinoline ring of 1 to study the effects of greater conformational fluidity on a receptor binding. The sigma(2) affinity of the open-ring compound decreased by 1700-fold, while a, affinity was not changed. Thus, a constrained tetrahydroisoquinoline ring system is key to the exceptional sigma(2) receptor binding affinity and selectivity of this active series. (c) 2007 Elsevier Ltd. All rights reserved.