(S)-3-methyl-4-(2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine | 1207369-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: (S)-3-methyl-4-(2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine
• 英文别名: (3S)-3-methyl-4-[2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]morpholine
• CAS: 1207369-02-5
• 化学式: C₁₈H₂₁N₅O₃
• 分子量: 355.396
• InChiKey: OSBIUDJTZFRHNT-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  96.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-methyl-4-(2-(4-nitrophenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine 在 tin(II) chloride dihdyrate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-3-ethoxy-4-(4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenylamino)cyclobut-3-ene-1,2-dione
  参考文献：
  名称：

  Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

  摘要：

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.

  DOI：

  10.1021/ml3003132

文献信息

• [EN] PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS DE PYRIMIDINE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010014939A1

  公开（公告）日：2010-02-04

  Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

  揭示了公式I的化合物，包括立体异构体、几何异构体、互变异构体、溶剂合物、代谢物和其药学上可接受的盐，这些化合物在调节PIKK相关激酶信号传导方面很有用，例如mTOR，并用于治疗至少部分由PIKK信号传导途径失调引起的疾病（例如癌症）。
• PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Bergeron Philippe

  公开号：US20100069357A1

  公开（公告）日：2010-03-18

  Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

  本发明涉及I式化合物，包括其立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，其对调节PIKK相关激酶信号传导，例如mTOR，并用于治疗至少部分由PIKK信号通路失调介导的疾病（例如癌症）具有用处。
• Pyrimidine compounds, compositions and methods of use
  申请人：Genentech, Inc.

  公开号：US08163763B2

  公开（公告）日：2012-04-24

  Disclosed are compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

  本发明涉及公式I的化合物，包括立体异构体、几何异构体、互变异构体、溶剂化物、代谢物和药学上可接受的盐，其在调节PIKK相关激酶信号传导方面具有用途，例如mTOR，并用于治疗至少部分由PIKK信号通路失调引起的疾病（例如癌症）。
• US8163763B2
  申请人：——

  公开号：US8163763B2

  公开（公告）日：2012-04-24
• Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349
  作者：Zhonghua Pei、Elizabeth Blackwood、Lichuan Liu、Shiva Malek、Marcia Belvin、Michael F. T. Koehler、Daniel F. Ortwine、Huifen Chen、Frederick Cohen、Jane R. Kenny、Philippe Bergeron、Kevin Lau、Cuong Ly、Xianrui Zhao、Anthony A. Estrada、Tom Truong、Jennifer A. Epler、Jim Nonomiya、Lan Trinh、Steve Sideris、John Lesnick、Linda Bao、Ulka Vijapurkar、Sophie Mukadam、Suzanne Tay、Gauri Deshmukh、Yung-Hsiang Chen、Xiao Ding、Lori S. Friedman、Joseph P. Lyssikatos

  DOI：10.1021/ml3003132

  日期：2013.1.10

  Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.