1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)phenyl)-3-(4-(piperazin-1-yl)phenyl)urea | 1197170-01-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)phenyl)-3-(4-(piperazin-1-yl)phenyl)urea
• 英文别名: 1-[4-[4-[(3R)-3-methylmorpholin-4-yl]-6-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3,5-triazin-2-yl]phenyl]-3-(4-piperazin-1-ylphenyl)urea
• CAS: 1197170-01-6
• 化学式: C₃₁H₃₉N₉O₃
• 分子量: 585.709
• InChiKey: FFOSMKDQFMVOLX-QJYLRPAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-哌嗪基苯胺 、 生成 1-(4-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-((R)-3-methylmorpholino)-1,3,5-triazin-2-yl)phenyl)-3-(4-(piperazin-1-yl)phenyl)urea
  参考文献：
  名称：

  2-Arylureidophenyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines as highly potent and selective ATP competitive mTOR inhibitors: Optimization of human microsomal stability

  摘要：

  Isosteric replacement of one of the 3,5-ethylene-bridged morpholines in 2-arylureidophenyl-4,6-di(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines led to significant improvements in human microsomal stability. 3-R-Me-morpholine and tetrahydropyran were identified as preferred isosteres for the bridged morpholine. Combination of tetrahydropyran substitution with an N-Me-piperazinophenylureido group led to 27, that selectively suppressed mTOR biomarkers in vivo and possessed excellent efficacy in a murine xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.031

文献信息

• [EN] TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS<br/>[FR] COMPOSÉS DE TRIAZINE FORMANT DES INHIBITEURS DE PI3-KINASE ET MTOR
  申请人：WYETH CORP

  公开号：WO2009143317A1

  公开（公告）日：2009-11-26

  Compounds of formula (I) wherein: R1 is and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

  式(I)的化合物，其中：R1为某一定义的基团，R2，R4和R6-9也为某一定义的基团，以及其药学上可接受的盐和酯。这些化合物能够抑制PI3激酶和mTOR，并可用于治疗由PI3激酶和mTOR介导的疾病，例如多种癌症。本发明还揭示了制备和使用这些化合物的方法。还揭示了含有这些化合物的各种组合物。
• TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS
  申请人：Venkatesan Aranapakam Mudumbai

  公开号：US20090304692A1

  公开（公告）日：2009-12-10

  Compounds of formula I wherein: R 1 is and R 2 , R 4 , and R 6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.

  式I的化合物，其中： R1是定义如下的基团， R2，R4和R6-9是定义如下的基团， 其药学上可接受的盐和酯。这些化合物抑制PI3激酶和mTOR，并可用于治疗由PI3激酶和mTOR介导的疾病，例如各种癌症。本发明揭示了制备和使用这些化合物的方法。还揭示了包含本发明化合物的各种组合物。
• TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2300483A1

  公开（公告）日：2011-03-30
• 2-Arylureidophenyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines as highly potent and selective ATP competitive mTOR inhibitors: Optimization of human microsomal stability
  作者：Jeroen C. Verheijen、David J. Richard、Kevin Curran、Joshua Kaplan、Ker Yu、Arie Zask

  DOI：10.1016/j.bmcl.2010.02.031

  日期：2010.4

  Isosteric replacement of one of the 3,5-ethylene-bridged morpholines in 2-arylureidophenyl-4,6-di(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines led to significant improvements in human microsomal stability. 3-R-Me-morpholine and tetrahydropyran were identified as preferred isosteres for the bridged morpholine. Combination of tetrahydropyran substitution with an N-Me-piperazinophenylureido group led to 27, that selectively suppressed mTOR biomarkers in vivo and possessed excellent efficacy in a murine xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.