N-(2-Trifluoroacetamidophenyl)pyrrole | 112798-16-0

• 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-(2-Trifluoroacetamidophenyl)pyrrole
• 英文别名: 2,2,2-trifluoro-N-(2-pyrrol-1-ylphenyl)acetamide
• CAS: 112798-16-0
• 化学式: C₁₂H₉F₃N₂O
• 分子量: 254.211
• InChiKey: UXGFHVDYARKYQC-UHFFFAOYSA-N

物化性质

• 熔点：
  81-82 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  353.2±42.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 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：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-Trifluoroacetamidophenyl)pyrrole 以67%的产率得到
  参考文献：
  名称：

  CHEESEMAN, G. W. H.;VARVOUNIS, G., J. HETEROCYCL. CHEM., 24,(1987) N 4, 1157-1161

  摘要：

  DOI：
• 作为产物：
  描述：

  1-(2-氨基苯基)吡咯 、 三氟乙酸 在 三乙胺 、 三氯乙腈 、 三苯基膦 作用下， 以 乙腈 为溶剂， 生成 N-(2-Trifluoroacetamidophenyl)pyrrole
  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

文献信息

• Cheeseman, G. W. H.; Varvounis, G., Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1157 - 1161
  作者：Cheeseman, G. W. H.、Varvounis, G.

  DOI：——

  日期：——
• CHEESEMAN, G. W. H.;VARVOUNIS, G., J. HETEROCYCL. CHEM., 24,(1987) N 4, 1157-1161
  作者：CHEESEMAN, G. W. H.、VARVOUNIS, G.

  DOI：——

  日期：——
• Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-a]quinoxalines as new antiplasmodial agents
  作者：Nicolas Primas、Peggy Suzanne、Pierre Verhaeghe、Sébastien Hutter、Charline Kieffer、Michèle Laget、Anita Cohen、Julie Broggi、Jean-Charles Lancelot、Aurélien Lesnard、Patrick Dallemagne、Pascal Rathelot、Sylvain Rault、Patrice Vanelle、Nadine Azas

  DOI：10.1016/j.ejmech.2014.06.014

  日期：2014.8

  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.