3-(((三甲基甲硅烷基)乙炔基)-1,5-萘啶 | 1246088-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 3-(((三甲基甲硅烷基)乙炔基)-1,5-萘啶
• 英文名称: 3-((Trimethylsilyl)ethynyl)-1,5-naphthyridine
• 英文别名: trimethyl-[2-(1,5-naphthyridin-3-yl)ethynyl]silane
• CAS: 1246088-67-4
• 化学式: C₁₃H₁₄N₂Si
• 分子量: 226.353
• InChiKey: NQZJFDDEKHPDJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 危险类别码：
  R36
• 危险类别：
  IRRITANT
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  3-(((三甲基甲硅烷基)乙炔基)-1,5-萘啶 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.75h， 生成 3-ethynyl-1,5-naphthyridine
  参考文献：
  名称：

  Rapid Discovery of a Novel Series of Abl Kinase Inhibitors by Application of an Integrated Microfluidic Synthesis and Screening Platform

  摘要：

  Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC(50) > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.

  DOI：

  10.1021/jm400099d
• 作为产物：
  描述：

  三甲基乙炔基硅 、 alkaline earth salt of/the/ methylsulfuric acid 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.75h， 生成 3-(((三甲基甲硅烷基)乙炔基)-1,5-萘啶
  参考文献：
  名称：

  Rapid Discovery of a Novel Series of Abl Kinase Inhibitors by Application of an Integrated Microfluidic Synthesis and Screening Platform

  摘要：

  Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC(50) > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.

  DOI：

  10.1021/jm400099d

文献信息

• Rapid Discovery of a Novel Series of Abl Kinase Inhibitors by Application of an Integrated Microfluidic Synthesis and Screening Platform
  作者：Bimbisar Desai、Karen Dixon、Elizabeth Farrant、Qixing Feng、Karl R. Gibson、Willem P. van Hoorn、James Mills、Trevor Morgan、David M. Parry、Manoj K. Ramjee、Christopher N. Selway、Gary J. Tarver、Gavin Whitlock、Adrian G. Wright

  DOI：10.1021/jm400099d

  日期：2013.4.11

  Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC(50) > 8 against Abl kinase - both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.