2-(ethylcarbamoylamino)-N-pyridin-4-yl-3H-benzimidazole-5-carboxamide | 1430719-95-1

• 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-(ethylcarbamoylamino)-N-pyridin-4-yl-3H-benzimidazole-5-carboxamide
• CAS: 1430719-95-1
• 化学式: C₁₆H₁₆N₆O₂
• 分子量: 324.342
• InChiKey: RWDWSDNQLQMIMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-硝基-5-氯苯胺 在 tin(II) chloride dihdyrate 、 水 、 sodium hydride 、 溶剂黄146 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.17h， 生成 2-(ethylcarbamoylamino)-N-pyridin-4-yl-3H-benzimidazole-5-carboxamide
  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

文献信息

• Discovery of New Benzothiazole-Based Inhibitors of Breakpoint Cluster Region-Abelson Kinase Including the T315I Mutant
  作者：Seunghee Hong、Jinhee Kim、Sun-Mi Yun、Hyunseung Lee、Yoonsu Park、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm301891t

  日期：2013.5.9

  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.