2-methoxy-4-(3-phenylpropyl)benzaldehyde | 289889-77-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-methoxy-4-(3-phenylpropyl)benzaldehyde
• CAS: 289889-77-6
• 化学式: C₁₇H₁₈O₂
• 分子量: 254.329
• InChiKey: JYRAQIUHORLXFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methoxy-4-(3-phenylpropyl)benzaldehyde 在 lithium aluminium tetrahydride 、 ammonium acetate 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-[2-Methoxy-4-(3-phenyl-propyl)-phenyl]-1-methyl-ethylamine
  参考文献：
  名称：

  1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists

  摘要：

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.

  DOI：

  10.1021/jm9906062
• 作为产物：
  描述：

  4-羟基-2-甲氧基苯甲醛 在 吡啶 、 sodium hydroxide 、 1,1'-bis(diphenylphosphinoferrocene)Pd 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.83h， 生成 2-methoxy-4-(3-phenylpropyl)benzaldehyde
  参考文献：
  名称：

  1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists

  摘要：

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.

  DOI：

  10.1021/jm9906062

文献信息

• 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists
  作者：Cynthia S. Dowd、Katharine Herrick-Davis、Christina Egan、Ann DuPre、Carol Smith、Milt Teitler、Richard A. Glennon

  DOI：10.1021/jm9906062

  日期：2000.8.1

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.
• 1-[2-Methoxy-5-(3-phenylpropyl)]-2-aminopropane Unexpectedly Shows 5-HT_2A Serotonin Receptor Affinity and Antagonist Character
  作者：Jagadeesh B. Rangisetty、Małgorzata Dukat、Cynthia S. Dowd、Katharine Herrick-Davis、Ann DuPre、Sami Gadepalli、Milt Teitler、Curtis R. Kelley、Najam A. Sharif、Richard A. Glennon

  DOI：10.1021/jm0100739

  日期：2001.9.1

  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.