1-[[4-Amino-2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol | 1240218-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-[[4-Amino-2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol
• 英文别名: 1-[[4-amino-2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol
• CAS: 1240218-13-6
• 化学式: C₁₃H₁₇F₃N₂O
• 分子量: 274.286
• InChiKey: GRIPJABRKBYMSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  49.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[[4-Amino-2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol 、 3-碘-4-甲基苯甲酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以44%的产率得到N-(4-((4-hydroxypiperidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide
  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：

  1-(溴甲基)-4-硝基-2-(三氟甲基)苯 在 raney nickel (catcart) 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-[[4-Amino-2-(trifluoromethyl)phenyl]methyl]piperidin-4-ol
  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