5-(3-(bromomethyl)phenoxy)-2-chloro-1,3-dimethylbenzene | 1426937-27-0

• 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: 5-(3-(bromomethyl)phenoxy)-2-chloro-1,3-dimethylbenzene
• 英文别名: 5-[3-(Bromomethyl)phenoxy]-2-chloro-1,3-dimethylbenzene；5-[3-(bromomethyl)phenoxy]-2-chloro-1,3-dimethylbenzene
• CAS: 1426937-27-0
• 化学式: C₁₅H₁₄BrClO
• 分子量: 325.633
• InChiKey: LZXWPPRKXODGBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  吲哚 、 5-(3-(bromomethyl)phenoxy)-2-chloro-1,3-dimethylbenzene 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以3.6%的产率得到1-[[3-(4-Chloro-3,5-dimethylphenoxy)phenyl]methyl]indole
  参考文献：
  名称：

  Antitrypanosomal Lead Discovery: Identification of a Ligand-Efficient Inhibitor of Trypanosoma cruzi CYP51 and Parasite Growth

  摘要：

  Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety and efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure-activity relationships around a class of imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) and 4j (NEU704), which are potent against in vitro cultures of T. cruzi and are greater than 160-fold selective over host cells. We report in vitro drug metabolism and properties profiling of 4c and show that this chemotype inhibits the T. cruzi CYP51 enzyme, an observation confirmed by X-ray crystallographic analysis. We compare the binding orientation of 4c to that of other, previously reported inhibitors. We show that 4c displays a significantly better ligand efficiency and a shorter synthetic route over previously disclosed CYP51 inhibitors, and should therefore be considered a promising lead compound for further optimization.

  DOI：

  10.1021/jm400012e
• 作为产物：
  描述：

  4-氯-3,5-二甲基苯酚 在 copper(l) iodide 、 三甲基氯硅烷 、 N,N-二甲基甘氨酸 、 1,1,3,3-四甲基二硅氧烷 、 caesium carbonate 、 lithium bromide 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 16.0h， 生成 5-(3-(bromomethyl)phenoxy)-2-chloro-1,3-dimethylbenzene
  参考文献：
  名称：

  Antitrypanosomal Lead Discovery: Identification of a Ligand-Efficient Inhibitor of Trypanosoma cruzi CYP51 and Parasite Growth

  摘要：

  Chagas disease is caused by the intracellular protozoan parasite Trypanosomal cruzi, and current drugs are lacking in terms of desired safety and efficacy profiles. Following on a recently reported high-throughput screening campaign, we have explored initial structure-activity relationships around a class of imidazole-based compounds. This profiling has uncovered compounds 4c (NEU321) and 4j (NEU704), which are potent against in vitro cultures of T. cruzi and are greater than 160-fold selective over host cells. We report in vitro drug metabolism and properties profiling of 4c and show that this chemotype inhibits the T. cruzi CYP51 enzyme, an observation confirmed by X-ray crystallographic analysis. We compare the binding orientation of 4c to that of other, previously reported inhibitors. We show that 4c displays a significantly better ligand efficiency and a shorter synthetic route over previously disclosed CYP51 inhibitors, and should therefore be considered a promising lead compound for further optimization.

  DOI：

  10.1021/jm400012e