4-[1-(4-methoxyphenyl)prop-1-enyl]morpholine | 64274-08-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-[1-(4-methoxyphenyl)prop-1-enyl]morpholine
• CAS: 64274-08-4
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: JSYFHXZCRGJDED-UHFFFAOYSA-N

物化性质

• 沸点：
  390.9±41.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-[1-(4-methoxyphenyl)prop-1-enyl]morpholine 在 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 生成 1-(2-Fluorophenyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxylic acid
  参考文献：
  名称：

  N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors

  摘要：

  In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.

  DOI：

  10.1021/jm2000536
• 作为产物：
  描述：

  吗啉 、 对甲氧基苯丙酮 在 四氯化钛 、 magnesium sulfate 、 N,N-二异丙基乙胺 作用下， 以 甲苯 为溶剂， 生成 4-[1-(4-methoxyphenyl)prop-1-enyl]morpholine
  参考文献：
  名称：

  N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors

  摘要：

  In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.

  DOI：

  10.1021/jm2000536