4-amino-2,5-dimethoxybenzyl cyanide | 168699-65-8

• 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-amino-2,5-dimethoxybenzyl cyanide
• 英文别名: 2-(4-Amino-2,5-dimethoxyphenyl)acetonitrile
• CAS: 168699-65-8
• 化学式: C₁₀H₁₂N₂O₂
• 分子量: 192.217
• InChiKey: IROXYYDAECMZRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-2,5-dimethoxybenzyl cyanide 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 反应 36.0h， 以52%的产率得到2,5-dimethoxy-p-aminophenethylamine
  参考文献：
  名称：

  In Vivo and in Vitro Studies on the Neurotoxic Potential of 6-Hydroxydopamine Analogs

  摘要：

  In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as B-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with-the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [H-3]NE and [H-3]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (K-i = 12 +/- 0 mu M) than the NE uptake site (K-i = 51 +/- 1 mu M). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the K-i for [H-3]NE uptake blockade and the EC(50) for synaptosomal release of preloaded [H-3]NE for the eight analogs (R(2) = 0.96; for log:log plot, R(2) = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between K-i and EC(50) was shown for all eight analogs using [H-3]DA (R(2) = 0.92; for log:log plot, R(2) = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

  DOI：

  10.1021/jm00020a024
• 作为产物：
  描述：

  (2,5-Dimethoxy-4-nitro-phenyl)-acetonitrile 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以93%的产率得到4-amino-2,5-dimethoxybenzyl cyanide
  参考文献：
  名称：

  In Vivo and in Vitro Studies on the Neurotoxic Potential of 6-Hydroxydopamine Analogs

  摘要：

  In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as B-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with-the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [H-3]NE and [H-3]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (K-i = 12 +/- 0 mu M) than the NE uptake site (K-i = 51 +/- 1 mu M). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the K-i for [H-3]NE uptake blockade and the EC(50) for synaptosomal release of preloaded [H-3]NE for the eight analogs (R(2) = 0.96; for log:log plot, R(2) = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between K-i and EC(50) was shown for all eight analogs using [H-3]DA (R(2) = 0.92; for log:log plot, R(2) = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.

  DOI：

  10.1021/jm00020a024

文献信息

• In Vivo and in Vitro Studies on the Neurotoxic Potential of 6-Hydroxydopamine Analogs
  作者：Su Ma、Lorrie Lin、R. Raghavan、Pat Cohenour、Peter Y. T. Lin、Jennifer Bennett、Russell J. Lewis、Eric L. Enwall、Richard Kostrzewa

  DOI：10.1021/jm00020a024

  日期：1995.9

  In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as B-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with-the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [H-3]NE and [H-3]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (K-i = 12 +/- 0 mu M) than the NE uptake site (K-i = 51 +/- 1 mu M). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the K-i for [H-3]NE uptake blockade and the EC(50) for synaptosomal release of preloaded [H-3]NE for the eight analogs (R(2) = 0.96; for log:log plot, R(2) = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between K-i and EC(50) was shown for all eight analogs using [H-3]DA (R(2) = 0.92; for log:log plot, R(2) = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.