4-(4-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde | 1226854-18-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-(4-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde
• CAS: 1226854-18-7
• 化学式: C₂₁H₂₆N₄O₃
• 分子量: 382.462
• InChiKey: RXZMSDFOFFTFFE-UHFFFAOYSA-N

物化性质

• 沸点：
  649.0±55.0 °C(predicted)
• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  67.67
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-羟基-3(2H)-苯并呋喃酮 、 4-(4-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以60%的产率得到4-Hydroxy-2-[[1-methyl-4-[4-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)piperidin-1-yl]pyrrolo[2,3-b]pyridin-3-yl]methylidene]-1-benzofuran-3-one
  参考文献：
  名称：

  Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

  摘要：

  Wediscovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3K alpha. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3K gamma revealed the key hydrogen bonding interactions. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.135
• 作为产物：
  描述：

  8-氧杂-3-氮杂双环[3,2,1]辛烷 、 1-(3-formyl-1-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidine-4-carboxylic acid 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到4-(4-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde
  参考文献：
  名称：

  Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

  摘要：

  Wediscovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3K alpha. An X-ray co-crystal structure of one inhibitor with the mTOR-related PI3K gamma revealed the key hydrogen bonding interactions. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.135

文献信息

• 4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
  作者：Hwei-Ru Tsou、Gloria MacEwan、Gary Birnberg、Nan Zhang、Natasja Brooijmans、Lourdes Toral-Barza、Irwin Hollander、Semiramis Ayral-Kaloustian、Ker Yu

  DOI：10.1016/j.bmcl.2010.02.012

  日期：2010.4

  A series of 5-ureidobenzofuranones was discovered as potent and selective inhibitors of mTOR with good cellular activity. Molecular modeling studies revealed several hydrogen bond interactions of the ureido group with the enzyme at the ATP-binding site. Furthermore, modeling showed that the ureido group is best situated at C-5 of the benzofuranone. Syntheses of 4-ureido and 5-ureidobenzofuranones are presented. (C) 2010 Elsevier Ltd. All rights reserved.