3-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane | 1144080-80-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane
• 英文别名: 3-[6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane
• CAS: 1144080-80-7
• 化学式: C₂₀H₁₇F₃N₆O₂
• 分子量: 430.389
• InChiKey: YEOARSOUBSRKQM-UHFFFAOYSA-N

物化性质

• 密度：
  1.59±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  85.5
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-哌嗪基苯胺 、 3-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane 以 二氯甲烷 为溶剂， 生成 1-{4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-(4-piperazin-1-ylphenyl)urea
  参考文献：
  名称：

  Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: Discovery of highly potent and selective analogs with improved human microsomal stability

  摘要：

  A series of highly potent and selective pyrazolopyrimidine mTOR inhibitors which contain water-solubilizing groups attached to the 6-arylureidophenyl moiety have been prepared. Such derivatives displayed superior potency to those in which these appendages were attached to alternative sites. In comparison to unfunctionalized arylureido compounds, these analogs demonstrated enhanced cellular potency and significantly improved stability towards human microsomes, resulting in an mTOR inhibitor with impressive efficacy in a xenograft model with an intermittent dosing regimen. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.096
• 作为产物：
  描述：

  三光气 、 4-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]aniline 以 二氯甲烷 为溶剂， 生成 3-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: Discovery of highly potent and selective analogs with improved human microsomal stability

  摘要：

  A series of highly potent and selective pyrazolopyrimidine mTOR inhibitors which contain water-solubilizing groups attached to the 6-arylureidophenyl moiety have been prepared. Such derivatives displayed superior potency to those in which these appendages were attached to alternative sites. In comparison to unfunctionalized arylureido compounds, these analogs demonstrated enhanced cellular potency and significantly improved stability towards human microsomes, resulting in an mTOR inhibitor with impressive efficacy in a xenograft model with an intermittent dosing regimen. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.096

文献信息

• THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS
  申请人：Zask Arie

  公开号：US20090098086A1

  公开（公告）日：2009-04-16

  The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds.

  该发明涉及Formula (Ia)和Formula (IIa)的噻吡嘧啶和吡唑嘧啶化合物，或其药用可接受的盐，其中组成变量如本文所定义的那样，包括该化合物的组合物，以及制备和使用该化合物的方法。
• Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors
  申请人：Wyeth LLC

  公开号：US08129371B2

  公开（公告）日：2012-03-06

  The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds.

  本发明涉及以下式(Ia)和(IIa)的噻唑嘧啶和吡唑嘧啶化合物，或其药学上可接受的盐，其中组分变量如定义的那样，包括这些化合物的组合物，以及制备和使用这些化合物的方法。
• US8129371B2
  申请人：——

  公开号：US8129371B2

  公开（公告）日：2012-03-06
• Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: Discovery of highly potent and selective analogs with improved human microsomal stability
  作者：David J. Richard、Jeroen C. Verheijen、Kevin Curran、Joshua Kaplan、Lourdes Toral-Barza、Irwin Hollander、Judy Lucas、Ker Yu、Arie Zask

  DOI：10.1016/j.bmcl.2009.10.096

  日期：2009.12

  A series of highly potent and selective pyrazolopyrimidine mTOR inhibitors which contain water-solubilizing groups attached to the 6-arylureidophenyl moiety have been prepared. Such derivatives displayed superior potency to those in which these appendages were attached to alternative sites. In comparison to unfunctionalized arylureido compounds, these analogs demonstrated enhanced cellular potency and significantly improved stability towards human microsomes, resulting in an mTOR inhibitor with impressive efficacy in a xenograft model with an intermittent dosing regimen. (C) 2009 Elsevier Ltd. All rights reserved.