4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester | 1422773-11-2

• 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: 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[6-fluoro-3-[7-formyl-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazin-2-yl]indazol-1-yl]piperidine-1-carboxylate
• CAS: 1422773-11-2
• 化学式: C₃₀H₃₉FN₆O₄Si
• 分子量: 594.761
• InChiKey: VQMNHTUJMGNCBE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.28
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester 在 sodium chlorite 、 氨基磺酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.5h， 以90%的产率得到2-[1-(1-tert-butoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid
  参考文献：
  名称：

  Pyrrolopyrazines as Selective Spleen Tyrosine Kinase Inhibitors

  摘要：

  We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.

  DOI：

  10.1021/jm301720p
• 作为产物：
  描述：

  (2-溴-5H-吡咯并[2,3-B]吡嗪-7-基)甲醇 在 copper(l) iodide 、 Jones reagent 、 四(三苯基膦)钯 、 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 4.75h， 生成 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pyrrolopyrazines as Selective Spleen Tyrosine Kinase Inhibitors

  摘要：

  We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.

  DOI：

  10.1021/jm301720p

文献信息

• Pyrrolopyrazine kinase inhibitors
  申请人：Chen Shaoqing

  公开号：US08658646B2

  公开（公告）日：2014-02-25

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

  本发明涉及使用式I中新型吡咯吡嗪衍生物，其中变量如本文所述，其抑制JAK和SYK并且用于治疗自身免疫和炎症性疾病。
• PYRROLOPYRAZINE KINASE INHIBITORS
  申请人：Chen Shaoqing

  公开号：US20130059834A1

  公开（公告）日：2013-03-07

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

  本发明涉及使用新型吡咯吡嗪衍生物（式I）的使用，其中变量如此处所述，其抑制JAK和SYK并且适用于治疗自身免疫和炎症性疾病。
• Pyrrolopyrazines as Selective Spleen Tyrosine Kinase Inhibitors
  作者：Fernando Padilla、Niala Bhagirath、Shaoqing Chen、Eric Chiao、David M. Goldstein、Johannes C. Hermann、Jonathan Hsu、Joshua J. Kennedy-Smith、Andreas Kuglstatter、Cheng Liao、Wenjian Liu、Lee E. Lowrie、Kin Chun Luk、Stephen M. Lynch、John Menke、Linghao Niu、Timothy D. Owens、Counde O-Yang、Aruna Railkar、Ryan C. Schoenfeld、Michelle Slade、Sandra Steiner、Yun-Chou Tan、Armando G. Villaseñor、Ce Wang、Jutta Wanner、Wenwei Xie、Daigen Xu、Xiaohu Zhang、Mingyan Zhou、Matthew C. Lucas

  DOI：10.1021/jm301720p

  日期：2013.2.28

  We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.