3-(pyridin-3-ylethynyl)-1H-indazole | 1150101-34-0

• 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: 3-(pyridin-3-ylethynyl)-1H-indazole
• 英文别名: 3-(2-pyridin-3-ylethynyl)-2H-indazole
• CAS: 1150101-34-0
• 化学式: C₁₄H₉N₃
• 分子量: 219.246
• InChiKey: GZOXBNAYOLYVTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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：
  41.6
• 氢给体数：
  1
• 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92%的产率得到3-(pyridin-3-ylethynyl)-1H-indazole
  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
• [EN] PYRAZOLE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE PYRAZOLE EN TANT QU'INHIBITEURS DE KINASE
  申请人：BURNHAM INST MEDICAL RESEARCH

  公开号：WO2009059030A1

  公开（公告）日：2009-05-07

  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.
• 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.