2,2,2-trichloro-N-(5-methyl-2-(1H-pyrrol-1-yl)phenyl)acetamide | 1620494-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2,2,2-trichloro-N-(5-methyl-2-(1H-pyrrol-1-yl)phenyl)acetamide
• CAS: 1620494-91-8
• 化学式: C₁₃H₁₁Cl₃N₂O
• 分子量: 317.602
• InChiKey: IAONRFMFAAWKLH-UHFFFAOYSA-N

物化性质

• 沸点：
  422.0±45.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  34.03
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloro-N-(5-methyl-2-(1H-pyrrol-1-yl)phenyl)acetamide 在 三氯氧磷 作用下， 以 吡啶 为溶剂， 反应 4.0h， 以20%的产率得到3-methyl-6-(trichloromethyl)pyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents

  摘要：

  Thanks to a preliminary in vitro screening of several CCl3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-a]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-a]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-a]quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.

  DOI：

  10.1016/j.ejmech.2014.06.014
• 作为产物：
  描述：

  5-甲基-2-(1H-吡咯-1-基)苯胺 、 三氯乙酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.0h， 以46%的产率得到2,2,2-trichloro-N-(5-methyl-2-(1H-pyrrol-1-yl)phenyl)acetamide
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents

  摘要：

  Thanks to a preliminary in vitro screening of several CCl3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-a]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-a]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-a]quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.

  DOI：

  10.1016/j.ejmech.2014.06.014