(R)-ethyl 4-(6-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate | 1062172-17-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-ethyl 4-(6-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate
• 英文别名: ethyl 4-[6-[4-(ethylcarbamoylamino)phenyl]-4-[(3R)-3-methylmorpholin-4-yl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate
• CAS: 1062172-17-1
• 化学式: C₂₇H₃₆N₈O₄
• 分子量: 536.634
• InChiKey: ZJGZMIKREDOSOI-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  三光气 、 ethyl (R)-4-(6-(4-aminophenyl)-4-(3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate 、 乙胺 在 三乙胺 作用下， 生成 (R)-ethyl 4-(6-(4-(3-ethylureido)phenyl)-4-(3-methylmorpholino)-1H-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

文献信息

• PYRAZOLOPYRIMIDINE ANALOGS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS
  申请人：Zask Arie

  公开号：US20080234262A1

  公开（公告）日：2008-09-25

  The present invention relates to Pyrazolopyrimidine Analogs, methods of making Pyrazolopyrimidine Analogs, compositions comprising a Pyrazolopyrimidine Analog, and methods for treating mTOR-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog. The invention also relates to treating PI3K-related disorders comprising administering to a subject in need thereof an effective amount of a Pyrazolopyrimidine Analog.

  本发明涉及吡唑吡嘧啶类似物，制备吡唑吡嘧啶类似物的方法，包含吡唑吡嘧啶类似物的组合物，以及治疗mTOR相关疾病的方法，包括向需要的受试者施用有效量的吡唑吡嘧啶类似物。该发明还涉及治疗PI3K相关疾病的方法，包括向需要的受试者施用有效量的吡唑吡嘧啶类似物。
• 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.