2-[5-difluoromethoxy-1-(1-methyl-azetidin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide | 1422772-28-8

• 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-[5-difluoromethoxy-1-(1-methyl-azetidin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide
• 英文别名: N-tert-butyl-2-[5-(difluoromethoxy)-1-[(1-methylazetidin-3-yl)methyl]indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide
• CAS: 1422772-28-8
• 化学式: C₂₄H₂₇F₂N₇O₂
• 分子量: 483.521
• InChiKey: WLXLHHAZRRMMDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2-溴-5H-吡咯并[2,3-B]吡嗪-7-基)甲醇 在 sodium chlorite 、 potassium dihydrogenphosphate 、 copper(l) iodide 、 Jones reagent 、 四(三苯基膦)钯 、 氨基磺酸 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 caesium carbonate 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 2,2,2-三氟乙醇 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 115.0h， 生成 2-[5-difluoromethoxy-1-(1-methyl-azetidin-3-ylmethyl)-1H-indazol-3-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide
  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

• [EN] PYRROLOPYRAZINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRROLOPYRAZINE KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013030138A1

  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.

  本发明涉及式I的新型吡咯并吡嗪衍生物的使用，其中变量如本文所述定义，其抑制JAK和SYK，并可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：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。
• US8658646B2
  申请人：——

  公开号：US8658646B2

  公开（公告）日：2014-02-25
• 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.