1-(2-chloro-4-(trifluoromethyl)phenyl)-2-(3-cyclopropyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4H-1,2,4-triazol-4-yl)ethan-1-ol | 1616406-56-4

• 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: 1-(2-chloro-4-(trifluoromethyl)phenyl)-2-(3-cyclopropyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4H-1,2,4-triazol-4-yl)ethan-1-ol
• CAS: 1616406-56-4
• 化学式: C₂₀H₂₀ClF₃N₄O
• 分子量: 424.853
• InChiKey: OMCYZDXDPOKNGI-UHFFFAOYSA-N

物化性质

• 沸点：
  579.5±60.0 °C(predicted)
• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.97
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  55.87
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-4-(trifluoromethyl)phenyl)-2-(3-cyclopropyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4H-1,2,4-triazol-4-yl)ethan-1-ol 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以38.6%的产率得到2-(3-amino-5-cyclopropyl-4H-1,2,4-triazol-4-yl)-1-(2-chloro-4-(trifluoromethyl)phenyl)ethanol
  参考文献：
  名称：

  Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents

  摘要：

  Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure-activity relationship studies followed by pharmacokinetics optimization resulted in the identification of 23 as an attractive lead with good oral bioavailability. Compound 23 was found to be efficacious (ED90 of 28.6 mg.kg(-1)) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class.

  DOI：

  10.1021/jm500535j
• 作为产物：
  描述：

  3-cyclopropyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4H-1,2,4-triazole 在 sodium tetrahydroborate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 1-(2-chloro-4-(trifluoromethyl)phenyl)-2-(3-cyclopropyl-5-(2,5-dimethyl-1H-pyrrol-1-yl)-4H-1,2,4-triazol-4-yl)ethan-1-ol
  参考文献：
  名称：

  Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents

  摘要：

  Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure-activity relationship studies followed by pharmacokinetics optimization resulted in the identification of 23 as an attractive lead with good oral bioavailability. Compound 23 was found to be efficacious (ED90 of 28.6 mg.kg(-1)) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class.

  DOI：

  10.1021/jm500535j