(E)-1-(2-hydroxy-4,5-dimethylphenyl)-3-(4-(pyrrolidin-1-yl)phenyl)prop-2-en-1-one | 1353224-26-6

• 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: (E)-1-(2-hydroxy-4,5-dimethylphenyl)-3-(4-(pyrrolidin-1-yl)phenyl)prop-2-en-1-one
• CAS: 1353224-26-6
• 化学式: C₂₁H₂₃NO₂
• 分子量: 321.419
• InChiKey: ACIHUNHUIFAVQV-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.54
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (E)-1-(2-hydroxy-4,5-dimethylphenyl)-3-(4-(pyrrolidin-1-yl)phenyl)prop-2-en-1-one 在 碘 作用下， 以 二甲基亚砜 为溶剂， 以75%的产率得到6,7-dimethyl-2-(4-(pyrrolidin-1-yl)phenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Chemical Modification of the Multitarget Neuroprotective Compound Fisetin

  摘要：

  Many factors are implicated in age-related central nervous system (CNS) disorders, making it unlikely that modulating only a single factor will provide effective treatment. Perhaps a better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Recently, we identified an orally active, neuroprotective, and cognition-enhancing molecule, the flavonoid fisetin, that is effective in several animal models of CNS disorders. Fisetin has direct antioxidant activity and can also increase the intracellular levels of glutathione (GSH), the major endogenous antioxidant. In addition, fisetin has both neurotrophic and anti-inflammatory activity. However, its relatively high EC50 in cell based assays, low lipophilicity, high topological polar surface area (tPSA), and poor bioavailability suggest that there is room for medicinal chemical improvement. Here we describe a multitiered approach to screening that has allowed us to identify fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model while at the same time maintaining other key activities.

  DOI：

  10.1021/jm2012563
• 作为产物：
  描述：

  4-(1-吡咯啉基)苯甲醛 、 2'-羟基-4‘,5'-二甲基苯乙酮 在 barium(II) hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以44%的产率得到(E)-1-(2-hydroxy-4,5-dimethylphenyl)-3-(4-(pyrrolidin-1-yl)phenyl)prop-2-en-1-one
  参考文献：
  名称：

  Chemical Modification of the Multitarget Neuroprotective Compound Fisetin

  摘要：

  Many factors are implicated in age-related central nervous system (CNS) disorders, making it unlikely that modulating only a single factor will provide effective treatment. Perhaps a better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Recently, we identified an orally active, neuroprotective, and cognition-enhancing molecule, the flavonoid fisetin, that is effective in several animal models of CNS disorders. Fisetin has direct antioxidant activity and can also increase the intracellular levels of glutathione (GSH), the major endogenous antioxidant. In addition, fisetin has both neurotrophic and anti-inflammatory activity. However, its relatively high EC50 in cell based assays, low lipophilicity, high topological polar surface area (tPSA), and poor bioavailability suggest that there is room for medicinal chemical improvement. Here we describe a multitiered approach to screening that has allowed us to identify fisetin derivatives with significantly enhanced activity in an in vitro neuroprotection model while at the same time maintaining other key activities.

  DOI：

  10.1021/jm2012563