2-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N,N-dimethylethanamine | 1144080-06-7

• 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: 2-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N,N-dimethylethanamine
• 英文别名: 2-[6-chloro-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]-N,N-dimethylethanamine
• CAS: 1144080-06-7
• 化学式: C₁₅H₂₁ClN₆O
• 分子量: 336.824
• InChiKey: SPNBEJKSCORJPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N,N-dimethylethanamine 、 4-氨基苯硼酸频哪醇酯 在 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2-(dimethylamino)ethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline
  参考文献：
  名称：

  吡唑并嘧啶类是雷帕霉素（mTOR）哺乳动物靶标的高效和选择性，ATP竞争性抑制剂：1-取代基的优化

  摘要：

  制备了一系列吡唑并嘧啶的哺乳动物雷帕霉素靶标（mTOR）抑制剂，这些抑制剂在1位具有多个取代基，从而产生具有出色效价，选择性和微粒体稳定性的化合物。将1-环己基缩酮基团与4-位的2,6-乙烯桥连吗啉和6-位脲基上的脲基苯基基团结合，可产生化合物8a，其在体内选择性抑制关键的mTOR生物标记至少8 h静脉给药并在异种移植肿瘤模型中显示出优异的口服活性。

  DOI：

  10.1016/j.bmcl.2009.12.086
• 作为产物：
  描述：

  N,N-二甲基乙醇胺 、 6-chloro-4-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 2.08h， 生成 2-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-N,N-dimethylethanamine
  参考文献：
  名称：

  THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS

  摘要：

  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。

  公开号：

  US20090098086A1

文献信息

• 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。
• 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.
• US8129371B2
  申请人：——

  公开号：US8129371B2

  公开（公告）日：2012-03-06
• [EN] THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS<br/>[FR] COMPOSÉS THIÉNOPYRIMIDINE ET PYRAZOLOPYRIMIDINE ET LEUR UTILISATION EN TANT QUE DES INHIBITEURS DE LA KINASE MTOR ET DE LA KINASE PI3
  申请人：WYETH CORP

  公开号：WO2009052145A1

  公开（公告）日：2009-04-23

  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.
• Pyrazolopyrimidines as highly potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR): Optimization of the 1-substituent
  作者：Kevin J. Curran、Jeroen C. Verheijen、Joshua Kaplan、David J. Richard、Lourdes Toral-Barza、Irwin Hollander、Judy Lucas、Semiramis Ayral-Kaloustian、Ker Yu、Arie Zask

  DOI：10.1016/j.bmcl.2009.12.086

  日期：2010.2

  A series of pyrazolopyrimidine mammalian Target Of Rapamycin (mTOR) inhibitors with various substituents at the 1-position have been prepared, resulting in compounds with excellent potency, selectivity and microsomal stability. Combination of a 1-cyclohexyl ketal group with a 2,6-ethylene bridged morpholine in the 4-position and a ureidophenyl group in the 6-positon resulted in compound 8a, that selectively

  制备了一系列吡唑并嘧啶的哺乳动物雷帕霉素靶标（mTOR）抑制剂，这些抑制剂在1位具有多个取代基，从而产生具有出色效价，选择性和微粒体稳定性的化合物。将1-环己基缩酮基团与4-位的2,6-乙烯桥连吗啉和6-位脲基上的脲基苯基基团结合，可产生化合物8a，其在体内选择性抑制关键的mTOR生物标记至少8 h静脉给药并在异种移植肿瘤模型中显示出优异的口服活性。