3-(6-methoxy-1H-indol-2-yl)-1H-pyrazolo[4,3-b]pyridine | 1259851-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 3-(6-methoxy-1H-indol-2-yl)-1H-pyrazolo[4,3-b]pyridine
• CAS: 1259851-23-4
• 化学式: C₁₅H₁₂N₄O
• 分子量: 264.286
• InChiKey: PRASIGARSOSUQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  66.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 水 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3-(6-methoxy-1H-indol-2-yl)-1H-pyrazolo[4,3-b]pyridine
  参考文献：
  名称：

  Identification of potent ITK inhibitors through focused compound library design including structural information

  摘要：

  A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.119

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.