2-ethynyl-5H-pyrrolo[2,3-b]pyrazine | 1184852-54-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: 2-ethynyl-5H-pyrrolo[2,3-b]pyrazine
• CAS: 1184852-54-7
• 化学式: C₈H₅N₃
• 分子量: 143.148
• InChiKey: IBWXZMKHXSGNDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• 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

• 作为反应物：
  描述：

  氯化二乙基铝 、 2-ethynyl-5H-pyrrolo[2,3-b]pyrazine 、 三甲基乙酰氯 、 碳酸氢钠 在 乙酸乙酯 、 水 、 magnesium sulfate 、 Silica gel 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.5h， 以Silica gel chromatography (20->60% EtOAc/hexanes) afforded 0.180 g (12%) of 1-(2-ethynyl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one as a brown solid的产率得到
  参考文献：
  名称：

  Pyrrolopyrazine kinase inhibitors

  摘要：

  本发明涉及使用式I的新型吡咯吡嗪衍生物，其中变量Q和R如本文所述，可以抑制JAK和SYK，并且可用于治疗自身免疫和炎症性疾病。

  公开号：

  US20090215750A1
• 作为产物：
  描述：

  在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 0.75h， 生成 2-ethynyl-5H-pyrrolo[2,3-b]pyrazine
  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

• PYRROLOPYRAZINE KINASE INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2247592A1

  公开（公告）日：2010-11-10
• US7939531B2
  申请人：——

  公开号：US7939531B2

  公开（公告）日：2011-05-10
• US8119636B2
  申请人：——

  公开号：US8119636B2

  公开（公告）日：2012-02-21
• [EN] PYRROLOPYRAZINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PYRROLOPYRAZINE KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009106442A1

  公开（公告）日：2009-09-03

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula (I), wherein the variables Q and R are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.
• [EN] PYRROLOPYRAZINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE PYRROLOPYRAZINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009106444A1

  公开（公告）日：2009-09-03

  The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables Q and R are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.