tert-butyl 5-amino-3-(1-(tert-butoxycarbonyl)-6-methyl-1H-indol-2-yl)-1H-indazole-1-carboxylate | 1294514-39-8

• 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: tert-butyl 5-amino-3-(1-(tert-butoxycarbonyl)-6-methyl-1H-indol-2-yl)-1H-indazole-1-carboxylate
• CAS: 1294514-39-8
• 化学式: C₂₆H₃₀N₄O₄
• 分子量: 462.549
• InChiKey: PYTKBGOBPWGEPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  34.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101.37
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-amino-3-(1-(tert-butoxycarbonyl)-6-methyl-1H-indol-2-yl)-1H-indazole-1-carboxylate 在 水 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 为溶剂， 反应 15.0h， 生成 2-methoxy-N-(3-(6-methyl-1H-indol-2-yl)-1H-indazol-5-yl)acetamide
  参考文献：
  名称：

  Optimisation of ITK inhibitors through successive iterative design cycles

  摘要：

  Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 mouse model. The intravenous administration of highly potent ITK inhibitor 11o resulted in dose-dependent, efficient suppression of IL-2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.035
• 作为产物：
  描述：

  3-碘-5-硝基-1H-吲唑 在 4-二甲氨基吡啶 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 tert-butyl 5-amino-3-(1-(tert-butoxycarbonyl)-6-methyl-1H-indol-2-yl)-1H-indazole-1-carboxylate
  参考文献：
  名称：

  Optimisation of ITK inhibitors through successive iterative design cycles

  摘要：

  Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 mouse model. The intravenous administration of highly potent ITK inhibitor 11o resulted in dose-dependent, efficient suppression of IL-2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.035