1-ethyl-3-(3-(6-methyl-1H-indol-2-yl)-1H-indazol-5-yl)urea | 1294514-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-ethyl-3-(3-(6-methyl-1H-indol-2-yl)-1H-indazol-5-yl)urea
• 英文别名: 1-ethyl-3-[3-(6-methyl-1H-indol-2-yl)-1H-indazol-5-yl]urea
• CAS: 1294514-14-9
• 化学式: C₁₉H₁₉N₅O
• 分子量: 333.393
• InChiKey: DHGXDLWTMDTFHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  85.6
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 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 、 水 、 氢气 、 potassium carbonate 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 1-ethyl-3-(3-(6-methyl-1H-indol-2-yl)-1H-indazol-5-yl)urea
  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

文献信息

• Optimisation of ITK inhibitors through successive iterative design cycles
  作者：Matthias Herdemann、Alexander Weber、Jérôme Jonveaux、Frank Schwoebel、Michael Stoeck、Isabelle Heit

  DOI：10.1016/j.bmcl.2011.01.035

  日期：2011.3

  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.