[2-(3-Bromo-phenyl)-ethyl]-methyl-(2-pyrrolidin-1-yl-ethyl)-amine | 710274-81-0

• 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: [2-(3-Bromo-phenyl)-ethyl]-methyl-(2-pyrrolidin-1-yl-ethyl)-amine
• 英文别名: 2-(3-bromophenyl)-N-methyl-N-(2-pyrrolidin-1-ylethyl)ethanamine
• CAS: 710274-81-0
• 化学式: C₁₅H₂₃BrN₂
• 分子量: 311.265
• InChiKey: BVKIRWQJJUCRGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [2-(3-Bromo-phenyl)-ethyl]-methyl-(2-pyrrolidin-1-yl-ethyl)-amine 在 正丁基锂 、 sodium iodide 、 三丁基氯化锡 作用下， 生成 <123I>-N-<2-(3-iodophenyl)ethyl>-N-methyl-2-(1-pyrrolidinyl)etylamine
  参考文献：
  名称：

  Synthesis and binding characteristics of potential SPECT imaging agents for .sigma.-1 and .sigma.-2 binding sites

  摘要：

  2-,3-, and 4-iodophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma1 and sigma2 subtypes in vitro. Sigma-1 binding affinity was determined by measuring competition with [H-3]-(+)-pentazocine binding to guinea pig brain membranes while sigma2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(l-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4-dichloro substituents of 1. In this series of compounds, K(i)'s at the al site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(l-pyrrolidinyl)ethylamine (4). K(i)'s for a2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma2/a, ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma1 sites; no such trend was observed at sigma2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with I-123. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with (NaI)-I-123 in the presence of excess CH3CO3H furnished [I-123]-2 and [I-123]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [I-123]-3 indicated up to 97% specific binding with guinea pig brain membranes.

  DOI：

  10.1021/jm00057a006
• 作为产物：
  描述：

  N-甲基-(2-吡咯烷-1-基-乙基)-胺 在 aluminium hydride 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 生成 [2-(3-Bromo-phenyl)-ethyl]-methyl-(2-pyrrolidin-1-yl-ethyl)-amine
  参考文献：
  名称：

  Synthesis and binding characteristics of potential SPECT imaging agents for .sigma.-1 and .sigma.-2 binding sites

  摘要：

  2-,3-, and 4-iodophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma1 and sigma2 subtypes in vitro. Sigma-1 binding affinity was determined by measuring competition with [H-3]-(+)-pentazocine binding to guinea pig brain membranes while sigma2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(l-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4-dichloro substituents of 1. In this series of compounds, K(i)'s at the al site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(l-pyrrolidinyl)ethylamine (4). K(i)'s for a2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma2/a, ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma1 sites; no such trend was observed at sigma2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with I-123. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with (NaI)-I-123 in the presence of excess CH3CO3H furnished [I-123]-2 and [I-123]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [I-123]-3 indicated up to 97% specific binding with guinea pig brain membranes.

  DOI：

  10.1021/jm00057a006

文献信息

• Synthesis and binding characteristics of potential SPECT imaging agents for .sigma.-1 and .sigma.-2 binding sites
  作者：Xiao Shu He、Wayne D. Bowen、Kan Sam Lee、Wanda Williams、Daniel R. Weinberger、Brian R. De Costa

  DOI：10.1021/jm00057a006

  日期：1993.3

  2-,3-, and 4-iodophenyl derivatives of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (1) were synthesized in two to four steps starting from N-methyl-2-(1-pyrrolidinyl)ethylamine. These compounds were evaluated for their capacity to label both sigma1 and sigma2 subtypes in vitro. Sigma-1 binding affinity was determined by measuring competition with [H-3]-(+)-pentazocine binding to guinea pig brain membranes while sigma2 binding was evaluated through competition with [3H]DTG binding to rat liver membranes in the presence of excess dextrallorphan. The binding data revealed that N-[2-(3-iodophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2) and N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(l-pyrrolidinyl)ethylamine (3) displayed almost identical binding affinity at sigma1 sites to the parent compound 1. This suggests that the 3- or 4-iodo group can effectively substitute for the 3,4-dichloro substituents of 1. In this series of compounds, K(i)'s at the al site varied from 2.0 nM for N-(4-iodobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (6) to 26.6 nM for N-(2-iodobenzyl)-N-methyl-2-(l-pyrrolidinyl)ethylamine (4). K(i)'s for a2 site ranged from 8.1 nM for 1 to 220 nM for N-(3-bromobenzyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine (11) while the sigma2/a, ratio varied from 1.8 for 4 to 25 for 11. Comparing halogen substitution, the trend Cl = I > Br > F was observed for binding affinity at sigma1 sites; no such trend was observed at sigma2 sites. On the basis of the binding data, compounds 2 and 3 were selected for labeling with I-123. Thus, treatment of the corresponding 3- and 4-(tributylstannyl) intermediates (7 and 8) with (NaI)-I-123 in the presence of excess CH3CO3H furnished [I-123]-2 and [I-123]-3 in up to 70% radiochemical yield. Preliminary in vitro binding with [I-123]-3 indicated up to 97% specific binding with guinea pig brain membranes.