N,N-dimethyl-3-(4-nitrophenoxy)benzamide | 1383627-55-1

• 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,N-dimethyl-3-(4-nitrophenoxy)benzamide
• CAS: 1383627-55-1
• 化学式: C₁₅H₁₄N₂O₄
• 分子量: 286.287
• InChiKey: SIZOLSPVLIWSDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  21.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.68
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-3-(4-nitrophenoxy)benzamide 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以85%的产率得到3-(4-aminophenoxy)-N,N-dimethylbenzamide
  参考文献：
  名称：

  Life Beyond Kinases: Structure-Based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors

  摘要：

  Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an "induced-fit" protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib, has shown unexpected promiscuous 5-HTRs binding affinities, K-i = 1959, 56, and 417 nM against 5-HT2A, 5-HT2B, and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its "off-target" 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.

  DOI：

  10.1021/jm300338m
• 作为产物：
  描述：

  ethyl 3-(4'-nitrophenoxy)benzoate 在 氯化亚砜 、 lithium hydroxide monohydrate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 9.0h， 生成 N,N-dimethyl-3-(4-nitrophenoxy)benzamide
  参考文献：
  名称：

  Life Beyond Kinases: Structure-Based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors

  摘要：

  Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an "induced-fit" protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib, has shown unexpected promiscuous 5-HTRs binding affinities, K-i = 1959, 56, and 417 nM against 5-HT2A, 5-HT2B, and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its "off-target" 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.

  DOI：

  10.1021/jm300338m