4-(3-chloro-2-methylphenyl)-6-((4-chlorophenyl)(methoxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methylquinolin-2(1H)-one trifluoroacetate | 1118761-96-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 4-(3-chloro-2-methylphenyl)-6-((4-chlorophenyl)(methoxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methylquinolin-2(1H)-one trifluoroacetate
• 英文别名: 4-(3-Chloro-2-methylphenyl)-6-[(4-chlorophenyl)-methoxy-(3-methylimidazol-4-yl)methyl]-1-methylquinolin-2-one;2,2,2-trifluoroacetic acid
• CAS: 1118761-96-8
• 化学式: C₂HF₃O₂*C₂₉H₂₅Cl₂N₃O₂
• 分子量: 632.466
• InChiKey: UMNVKXYXTGRENR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  43
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(3-chloro-2-methylphenyl)-6-((4-chlorophenyl)(methoxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methylquinolin-2(1H)-one 、 三氟乙酸 以 甲醇 、 水 为溶剂， 反应 0.5h， 以56.5 mg的产率得到4-(3-chloro-2-methylphenyl)-6-((4-chlorophenyl)(methoxy)(1-methyl-1H-imidazol-5-yl)methyl)-1-methylquinolin-2(1H)-one trifluoroacetate
  参考文献：
  名称：

  Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease

  摘要：

  Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14 alpha-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.

  DOI：

  10.1021/jm801313t