(Z)-3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-1-methyl-5-nitroindolin-2-one | 1311143-79-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (Z)-3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-1-methyl-5-nitroindolin-2-one
• 英文别名: (3Z)-3-[(2-ethyl-5-methyl-1H-imidazol-4-yl)methylidene]-1-methyl-5-nitroindol-2-one
• CAS: 1311143-79-9
• 化学式: C₁₆H₁₆N₄O₃
• 分子量: 312.328
• InChiKey: HJMRIPSQOHUEGT-WQLSENKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-1-methyl-5-nitroindolin-2-one 在 氯化铵 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.17h， 以71%的产率得到(Z)-5-amino-3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-1-methylindolin-2-one
  参考文献：
  名称：

  Irreversible Nek2 Kinase Inhibitors with Cellular Activity

  摘要：

  A structure-based approach was used to design irreversible, cysteine-targeted inhibitors of the human centrosomal kinase, Nek2. Potent inhibition of Nek2 kinase activity in biochemical and cell-based assays required a noncatalytic cysteine residue (Cys22), located near the glycine-rich loop in a subset of human kinases. Elaboration of an oxindole scaffold led to our most selective compound, oxindole propynamide 16 (JH295). Propynamide 16 irreversibly inhibited cellular Nek2 without affecting the mitotic kinases, Cdk1, Aurora B, or Plk1. Moreover, 16 did not perturb bipolar spindle assembly or the spindle assembly checkpoint. To our knowledge, 16 is the first small molecule shown to inactivate Nek2 kinase activity in cells.

  DOI：

  10.1021/jm200222m
• 作为产物：
  描述：

  N-甲基吲哚酮 在 哌啶 、 硫酸 、 硝酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 18.5h， 生成 (Z)-3-((2-ethyl-4-methyl-1H-imidazol-5-yl)methylene)-1-methyl-5-nitroindolin-2-one
  参考文献：
  名称：

  Irreversible Nek2 Kinase Inhibitors with Cellular Activity

  摘要：

  A structure-based approach was used to design irreversible, cysteine-targeted inhibitors of the human centrosomal kinase, Nek2. Potent inhibition of Nek2 kinase activity in biochemical and cell-based assays required a noncatalytic cysteine residue (Cys22), located near the glycine-rich loop in a subset of human kinases. Elaboration of an oxindole scaffold led to our most selective compound, oxindole propynamide 16 (JH295). Propynamide 16 irreversibly inhibited cellular Nek2 without affecting the mitotic kinases, Cdk1, Aurora B, or Plk1. Moreover, 16 did not perturb bipolar spindle assembly or the spindle assembly checkpoint. To our knowledge, 16 is the first small molecule shown to inactivate Nek2 kinase activity in cells.

  DOI：

  10.1021/jm200222m