3-iodo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-6-carbaldehyde | 1168720-54-4

• 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-iodo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-6-carbaldehyde
• 英文别名: 3-iodo-2-(2-(trimethylsilyl)ethyl)-2H-indazole-6-carbaldehyde；3-Iodo-2-(2-trimethylsilylethoxymethyl)indazole-6-carbaldehyde
• CAS: 1168720-54-4
• 化学式: C₁₄H₁₉IN₂O₂Si
• 分子量: 402.307
• InChiKey: YZMKFGBUQABGQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1H-吲唑-6-甲醛 在 四丁基溴化铵 、 碘 、 potassium carbonate 、 potassium hydroxide 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-6-carbaldehyde 、 3-iodo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-6-carbaldehyde
  参考文献：
  名称：

  [EN] KINASE INHIBITORS AND METHOD OF TREATING CANCER WITH SAME
  [FR] INHIBITEURS DE KINASES ET PROCÉDÉ DE TRAITEMENT DU CANCER UTILISANT CEUX-CI

  摘要：

  公开号：

  WO2011123946A8

文献信息

• Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides
  作者：Radoslaw Laufer、Grace Ng、Yong Liu、Narendra Kumar B. Patel、Louise G. Edwards、Yunhui Lang、Sze-Wan Li、Miklos Feher、Don E. Awrey、Genie Leung、Irina Beletskaya、Olga Plotnikova、Jacqueline M. Mason、Richard Hodgson、Xin Wei、Guodong Mao、Xunyi Luo、Ping Huang、Erin Green、Reza Kiarash、Dan Chi-Chia Lin、Marees Harris-Brandts、Fuqiang Ban、Vincent Nadeem、Tak W. Mak、Guohua J. Pan、Wei Qiu、Nickolay Y. Chirgadze、Henry W. Pauls

  DOI：10.1016/j.bmc.2014.06.027

  日期：2014.9

  TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50=3.6nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.
• [EN] INDAZOLYL, BENZIMIDAZOLYL, BENZOTRIAZOLYL SUBSTITUTED INDOLINONE DERIVATIVES AS KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS D'INDOLMONE À SUBSTITUTION INDAZOLYLE, BENZIMIDAZOLYLE, BENZOTRIAZOLYLE EN TANT QU'INHIBITEURS DE KINASES UTILISÉS DANS LE TRAITEMENT DU CANCER
  申请人：UNIV HEALTH NETWORK

  公开号：WO2009079767A9

  公开（公告）日：2009-10-01
• The Discovery of PLK4 Inhibitors: (<i>E</i>)-3-((1<i>H</i>-Indazol-6-yl)methylene)indolin-2-ones as Novel Antiproliferative Agents
  作者：Radoslaw Laufer、Bryan Forrest、Sze-Wan Li、Yong Liu、Peter Sampson、Louise Edwards、Yunhui Lang、Donald E. Awrey、Guodong Mao、Olga Plotnikova、Genie Leung、Richard Hodgson、Irina Beletskaya、Jacqueline M. Mason、Xunyi Luo、Xin Wei、Yi Yao、Miklos Feher、Fuqiang Ban、Reza Kiarash、Erin Green、Tak W. Mak、Guohua Pan、Henry W. Pauls

  DOI：10.1021/jm400380m

  日期：2013.8.8

  The family of Polo-like kinases is important in the regulation of mitotic progression; this work keys on one member, namely Polo-like kinase 4 (PLK4). PLK4 has been identified as a candidate anticancer target which prompted a search for potent and selective inhibitors of PLK4. The body of the paper describes lead generation and optimization work which yielded nanomolar PLK4 inhibitors. Lead generation began with directed virtual screening, using a ligand-based focused library and a PLK4 homology model. Validated hits were used as starting points for the design and discovery of PLK4 inhibitors of novel structure, namely (E)-3-((1H-indazol-6-yl)methylene)indolin-2-ones. Computational models, based on a published X-ray structure (PLK4 kinase domain), were used to understand and optimize the in vitro activity of the series; potent antiproliferative activity was obtained. The kinase selectivity profile and cell cycle analysis of selected inhibitors are described. The results of a xenograft study with an optimized compound 50 (designated CFI-400437) support the potential of these novel PLK4 inhibitors for cancer therapy.