(5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxylic acid | 1428184-02-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxylic acid
• CAS: 1428184-02-4
• 化学式: C₂₀H₁₇F₃N₂O₃
• 分子量: 390.362
• InChiKey: RRTOJLFXSHKZHM-OQLLNIDSSA-N

物化性质

• 熔点：
  270 °C
• 沸点：
  560.3±50.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.33
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxylic acid 在 N,N'-羰基二咪唑 、 氨 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.5h， 以84%的产率得到(5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials

  摘要：

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.

  DOI：

  10.1021/jm400009c
• 作为产物：
  描述：

  tert-butyl 5-methyl-3-oxo-1,2-dihydropyrrole-4-carboxylate 在 盐酸 、 potassium hydrogensulfate 作用下， 以 乙醇 、 水 为溶剂， 反应 6.0h， 生成 (5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-2-methyl-4-oxo-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials

  摘要：

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.

  DOI：

  10.1021/jm400009c