(+/-)-N-trifluoroacetyl-1-(2-methoxyphenyl)-2-aminopropane | 370884-68-7

• 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: (+/-)-N-trifluoroacetyl-1-(2-methoxyphenyl)-2-aminopropane
• 英文别名: Methoxyphenamine N-TFA；2,2,2-trifluoro-N-[1-(2-methoxyphenyl)propan-2-yl]acetamide
• CAS: 370884-68-7
• 化学式: C₁₂H₁₄F₃NO₂
• 分子量: 261.244
• InChiKey: NNEDLYGLYQTJFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-N-trifluoroacetyl-1-(2-methoxyphenyl)-2-aminopropane 在 10percent Pd/C 氢气 、 四氯化钛 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、310.27 kPa 条件下， 反应 77.5h， 生成 2,2,2-trifluoro-N-[1-[2-methoxy-5-(3-phenylpropyl)phenyl]propan-2-yl]acetamide
  参考文献：
  名称：

  1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character

  摘要：

  Certain phenylethylamines, such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a), are high-affinity 5-HT2 agonists. Previous structure-affinity studies have concluded that both the 2,5-dimethoxy substitution pattern and the nature of substituents at the 4-position are important determinants of high affinity. We recently demonstrated that replacement of the bromo group of DOB with a 3-(phenyl)propyl substituent results in retention of affinity and that, counter to established structure-affinity relationships, the 2,5-dimethoxy substitution pattern is no longer a requirement for the binding. The present investigation extends these findings by examining a series of analogues, 3, lacking a 5-methoxy group. It was additionally found that shifting the phenylalkyl substituent from the 4- to the 5-position (e.g., 4i) also results in retention of affinity. For example, 1-(2-methoxy-5-(3-phenylpropyl)-2-aminopropane (6; the alpha -methyl derivative of 4i) binds at 5-HT2A receptors with high affinity (K-i = 13 nM) and possesses 5-HT2A antagonist character. Thus, not only is the 2,5-dimethoxy substitution pattern not a requirement for the binding of certain phenylethylamines at 5-HT2A receptors, the presence of a 4-position substituent (previously thought to serve as a modulator of affinity of DOB-like agents) is also not required. Striking differences in the 5-HT2A binding requirements of the present compounds as compared to DOB-like agents suggest multiple substituent-dependent modes of binding.

  DOI：

  10.1021/jm0100739
• 作为产物：
  描述：

  1-(2-甲氧苯基)-2-丙胺 、 三氟乙酸酐 以 苯 为溶剂， 反应 2.0h， 以67%的产率得到(+/-)-N-trifluoroacetyl-1-(2-methoxyphenyl)-2-aminopropane
  参考文献：
  名称：

  1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character

  摘要：

  Certain phenylethylamines, such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a), are high-affinity 5-HT2 agonists. Previous structure-affinity studies have concluded that both the 2,5-dimethoxy substitution pattern and the nature of substituents at the 4-position are important determinants of high affinity. We recently demonstrated that replacement of the bromo group of DOB with a 3-(phenyl)propyl substituent results in retention of affinity and that, counter to established structure-affinity relationships, the 2,5-dimethoxy substitution pattern is no longer a requirement for the binding. The present investigation extends these findings by examining a series of analogues, 3, lacking a 5-methoxy group. It was additionally found that shifting the phenylalkyl substituent from the 4- to the 5-position (e.g., 4i) also results in retention of affinity. For example, 1-(2-methoxy-5-(3-phenylpropyl)-2-aminopropane (6; the alpha -methyl derivative of 4i) binds at 5-HT2A receptors with high affinity (K-i = 13 nM) and possesses 5-HT2A antagonist character. Thus, not only is the 2,5-dimethoxy substitution pattern not a requirement for the binding of certain phenylethylamines at 5-HT2A receptors, the presence of a 4-position substituent (previously thought to serve as a modulator of affinity of DOB-like agents) is also not required. Striking differences in the 5-HT2A binding requirements of the present compounds as compared to DOB-like agents suggest multiple substituent-dependent modes of binding.

  DOI：

  10.1021/jm0100739