4-(1-ethyl-1H-pyrazol-5-yl)benzene-1,2-diamine | 1430720-28-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(1-ethyl-1H-pyrazol-5-yl)benzene-1,2-diamine
• 英文别名: 4-(2-Ethylpyrazol-3-yl)benzene-1,2-diamine；4-(2-ethylpyrazol-3-yl)benzene-1,2-diamine
• CAS: 1430720-28-7
• 化学式: C₁₁H₁₄N₄
• 分子量: 202.259
• InChiKey: DDSHZLICJKQEAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  69.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-ethyl-3-(N-(ethylcarbamoyl)-C-methylsulfanylcarbonimidoyl)urea 、 4-(1-ethyl-1H-pyrazol-5-yl)benzene-1,2-diamine 在 溶剂黄146 作用下， 以 水 为溶剂， 反应 5.0h， 以50%的产率得到C₁₅H₁₈N₆O
  参考文献：
  名称：

  Discovery of New Benzothiazole-Based Inhibitors of Breakpoint Cluster Region-Abelson Kinase Including the T315I Mutant

  摘要：

  The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (Bcr-Abl) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant Bcr-Abl kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type Bcr-Abl and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant Bcr-Abl.

  DOI：

  10.1021/jm301891t
• 作为产物：
  描述：

  1-乙基吡唑-5-硼酸 、 4-溴邻苯二胺 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.5h， 生成 4-(1-ethyl-1H-pyrazol-5-yl)benzene-1,2-diamine
  参考文献：
  名称：

  Discovery of New Benzothiazole-Based Inhibitors of Breakpoint Cluster Region-Abelson Kinase Including the T315I Mutant

  摘要：

  The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (Bcr-Abl) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant Bcr-Abl kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type Bcr-Abl and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant Bcr-Abl.

  DOI：

  10.1021/jm301891t