2-((1H-indazol-3-yl)ethynyl)aniline | 1256346-62-9

• 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: 2-((1H-indazol-3-yl)ethynyl)aniline
• 英文别名: 2-[2-(2H-indazol-3-yl)ethynyl]aniline
• CAS: 1256346-62-9
• 化学式: C₁₅H₁₁N₃
• 分子量: 233.272
• InChiKey: MMBGCGZKLJHHNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以81%的产率得到2-((1H-indazol-3-yl)ethynyl)aniline
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of 3-Ethynyl-1H-indazoles as Inhibitors of the Phosphatidylinositol 3-Kinase Signaling Pathway

  摘要：

  A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibition against critical components of the PI3K pathway, targeting PI3K, PDK1, and mTOR kinases. A combination of computational modeling and structure-activity relationship studies reveals a possible novel mode for PI3K inhibition, resulting in a PI3K alpha isoform-specific compound. Hence, by targeting the most oncogenic mutant isoform of PI3K, the compound displays antiproliferative activity both in monolayer human cancer cell cultures and in three-dimensional tumor models. Because of its favorable physicochemical, in vitro ADME and drug-like properties, we propose that this novel ATP mimetic scaffold could prove useful in deriving novel selecting and multikinase inhibitors for clinical use.

  DOI：

  10.1021/jm100825h

文献信息

• Design, Synthesis, and Structure−Activity Relationships of 3-Ethynyl-1<i>H</i>-indazoles as Inhibitors of the Phosphatidylinositol 3-Kinase Signaling Pathway
  作者：Elisa Barile、Surya K. De、Coby B. Carlson、Vida Chen、Christine Knutzen、Megan Riel-Mehan、Li Yang、Russell Dahl、Gary Chiang、Maurizio Pellecchia

  DOI：10.1021/jm100825h

  日期：2010.12.9

  A new series of 3-ethynyl-1H-indazoles has been synthesized and evaluated in both biochemical and cell-based assays as potential kinase inhibitors. Interestingly, a selected group of compounds identified from this series exhibited low micromolar inhibition against critical components of the PI3K pathway, targeting PI3K, PDK1, and mTOR kinases. A combination of computational modeling and structure-activity relationship studies reveals a possible novel mode for PI3K inhibition, resulting in a PI3K alpha isoform-specific compound. Hence, by targeting the most oncogenic mutant isoform of PI3K, the compound displays antiproliferative activity both in monolayer human cancer cell cultures and in three-dimensional tumor models. Because of its favorable physicochemical, in vitro ADME and drug-like properties, we propose that this novel ATP mimetic scaffold could prove useful in deriving novel selecting and multikinase inhibitors for clinical use.