N-[5-bromo-2-(1H-pyrrol-1-yl)phenyl]-2,2,2-trichloroacetamide | 1620494-89-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-[5-bromo-2-(1H-pyrrol-1-yl)phenyl]-2,2,2-trichloroacetamide
• 英文别名: N-(5-bromo-2-pyrrol-1-ylphenyl)-2,2,2-trichloroacetamide
• CAS: 1620494-89-4
• 化学式: C₁₂H₈BrCl₃N₂O
• 分子量: 382.471
• InChiKey: PXUZUAQCVGMLOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-[5-bromo-2-(1H-pyrrol-1-yl)phenyl]-2,2,2-trichloroacetamide 在 三氯氧磷 作用下， 以 吡啶 为溶剂， 反应 4.0h， 以59%的产率得到3-bromo-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-bromo-2-(1H-pyrrol-1-yl)aniline 、 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63%的产率得到N-[5-bromo-2-(1H-pyrrol-1-yl)phenyl]-2,2,2-trichloroacetamide
  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