(3S)-4-[1-(1-benzylpiperidin-4-yl)-6-chloropyrazolo[3,4-d]pyrimidin-4-yl]-3-methylmorpholine | 1199878-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S)-4-[1-(1-benzylpiperidin-4-yl)-6-chloropyrazolo[3,4-d]pyrimidin-4-yl]-3-methylmorpholine
• CAS: 1199878-42-6
• 化学式: C₂₂H₂₇ClN₆O
• 分子量: 426.949
• InChiKey: QLGDLICOGCQKAL-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (3S)-4-[1-(1-benzylpiperidin-4-yl)-6-chloropyrazolo[3,4-d]pyrimidin-4-yl]-3-methylmorpholine 、 氯甲酸乙酯 在 1-氯乙基氯甲酸酯 作用下， 生成 ethyl 4-[6-chloro-4-[(3S)-3-methylmorpholin-4-yl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate
  参考文献：
  名称：

  Morpholine Derivatives Greatly Enhance the Selectivity of Mammalian Target of Rapamycin (mTOR) Inhibitors

  摘要：

  Dramatic improvements in mTOR-targeting selectivity were achieved by replacing morpholine in pyrazolopyrimidine inhibitors with bridged morpholines. Analogues with subnanomolar mTOR IC(50) values and up to 26000-fold selectivity versus PI3K alpha were prepared. Chiral morpholines gave inhibitors whose enantiomers had different selectivity and potency profiles. Molecular modeling suggests that a single amino acid difference between PI3K and mTOR (Phe961 Leu) accounts for the profound selectivity seen by creating a deeper pocket in mTOR that can accommodate bridged morpholines.

  DOI：

  10.1021/jm901415x
• 作为产物：
  描述：

  (S)-3-甲基吗啉 、 1-(1-benzylpiperidin-4-yl)-4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine 生成 (3S)-4-[1-(1-benzylpiperidin-4-yl)-6-chloropyrazolo[3,4-d]pyrimidin-4-yl]-3-methylmorpholine
  参考文献：
  名称：

  Morpholine Derivatives Greatly Enhance the Selectivity of Mammalian Target of Rapamycin (mTOR) Inhibitors

  摘要：

  Dramatic improvements in mTOR-targeting selectivity were achieved by replacing morpholine in pyrazolopyrimidine inhibitors with bridged morpholines. Analogues with subnanomolar mTOR IC(50) values and up to 26000-fold selectivity versus PI3K alpha were prepared. Chiral morpholines gave inhibitors whose enantiomers had different selectivity and potency profiles. Molecular modeling suggests that a single amino acid difference between PI3K and mTOR (Phe961 Leu) accounts for the profound selectivity seen by creating a deeper pocket in mTOR that can accommodate bridged morpholines.

  DOI：

  10.1021/jm901415x

文献信息

• Morpholine Derivatives Greatly Enhance the Selectivity of Mammalian Target of Rapamycin (mTOR) Inhibitors
  作者：Arie Zask、Joshua Kaplan、Jeroen C. Verheijen、David J. Richard、Kevin Curran、Natasja Brooijmans、Eric M. Bennett、Lourdes Toral-Barza、Irwin Hollander、Semiramis Ayral-Kaloustian、Ker Yu

  DOI：10.1021/jm901415x

  日期：2009.12.24

  Dramatic improvements in mTOR-targeting selectivity were achieved by replacing morpholine in pyrazolopyrimidine inhibitors with bridged morpholines. Analogues with subnanomolar mTOR IC(50) values and up to 26000-fold selectivity versus PI3K alpha were prepared. Chiral morpholines gave inhibitors whose enantiomers had different selectivity and potency profiles. Molecular modeling suggests that a single amino acid difference between PI3K and mTOR (Phe961 Leu) accounts for the profound selectivity seen by creating a deeper pocket in mTOR that can accommodate bridged morpholines.