3-(pyridin-4-ylethynyl)-1H-pyrazolo[3,4-b]pyridine | 1150101-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 3-(pyridin-4-ylethynyl)-1H-pyrazolo[3,4-b]pyridine
• 英文别名: 3-(2-pyridin-4-ylethynyl)-2H-pyrazolo[3,4-b]pyridine
• CAS: 1150101-78-2
• 化学式: C₁₃H₈N₄
• 分子量: 220.233
• InChiKey: JGQJFQCPRFMJSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 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：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  tert-butyl 3-(pyridin-4-ylethynyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以86%的产率得到3-(pyridin-4-ylethynyl)-1H-pyrazolo[3,4-b]pyridine
  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

• PYRAZOLE DERIVATIVES AS KINASE INHIBITORS
  申请人：Pellecchia Maurizio

  公开号：US20090124621A1

  公开（公告）日：2009-05-14

  The present invention provides compounds having the general structure I, or a pharmaceutically acceptable salt thereof: wherein X is a six-member ring selected from phenyl, pyridine, or pyrimidine; Y is H, an alkenyl, a substituted alkenyl, or alkynyl, and R is H or alkyl. Pharmaceutical compositions for treating various disorders such as cancers, the compositions including compound I are also provided.
• Pyrazole Derivatives as Kinase Inhibitors
  申请人：Pellecchia Maurizio

  公开号：US20110212961A1

  公开（公告）日：2011-09-01

  The present invention provides compounds having the general structure I, or a pharmaceutically acceptable salt thereof: wherein X is a six-member ring selected from phenyl, pyridine, or pyrimidine; Y is H, an alkenyl, a substituted alkenyl, or alkynyl, and R is H or alkyl. Pharmaceutical compositions for treating various disorders such as cancers, the compositions including compound I are also provided.
• US7951832B2
  申请人：——

  公开号：US7951832B2

  公开（公告）日：2011-05-31
• 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.