4-(4-(4-(2-hydroxyethyl)piperazine-1-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde | 1242772-52-6

• 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: 4-(4-(4-(2-hydroxyethyl)piperazine-1-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde
• CAS: 1242772-52-6
• 化学式: C₂₁H₂₉N₅O₃
• 分子量: 399.493
• InChiKey: RVCPWYGVXIIXKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.74
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  81.91
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-羟基-3(2H)-苯并呋喃酮 、 4-(4-(4-(2-hydroxyethyl)piperazine-1-carbonyl)piperidin-1-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 4-Hydroxy-2-[[4-[4-[4-(2-hydroxyethyl)piperazine-1-carbonyl]piperidin-1-yl]-1-methylpyrrolo[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：

  4-bromo-1-methyl-1-H-pyrrolo[2,3-b]pyridine-3-carbaldehyde 、 4-[4-(2-Hydroxyethyl)piperazine-1-carbonyl]piperidine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 dipotassium hydrogenphosphate 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 乙二醇二甲醚 为溶剂， 生成 4-(4-(4-(2-hydroxyethyl)piperazine-1-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