2-[4-(3-Methoxy-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic acid | 816450-56-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-[4-(3-Methoxy-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic acid
• 英文别名: 2-[4-(3-methoxyphenoxy)phenyl]-3H-benzimidazole-5-carboxylic acid
• CAS: 816450-56-3
• 化学式: C₂₁H₁₆N₂O₄
• 分子量: 360.369
• InChiKey: GDOTXWSIGNRCAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  84.44
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-[4-(3-Methoxy-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic acid 在 三溴化硼 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.5h， 生成 2-[4-(3-Hydroxy-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic acid amide
  参考文献：
  名称：

  Checkpoint Kinase Inhibitors:  SAR and Radioprotective Properties of a Series of 2-Arylbenzimidazoles

  摘要：

  The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenzimidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependently protects human CD4+ and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.

  DOI：

  10.1021/jm0495935
• 作为产物：
  描述：

  4-(3-甲氧基苯氧基)-苯甲醛 、 3,4-二氨基苯甲酸 在 sodium metabisulfite 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 6.5h， 生成 2-[4-(3-Methoxy-phenoxy)-phenyl]-1H-benzoimidazole-5-carboxylic acid
  参考文献：
  名称：

  Checkpoint Kinase Inhibitors:  SAR and Radioprotective Properties of a Series of 2-Arylbenzimidazoles

  摘要：

  The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenzimidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependently protects human CD4+ and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.

  DOI：

  10.1021/jm0495935