1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl) phenyl)urea | 1207358-27-7

• 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: 1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl) phenyl)urea
• 英文别名: 1-ethyl-3-[4-(4-morpholin-4-yl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl]urea
• CAS: 1207358-27-7
• 化学式: C₂₀H₂₆N₆O₂
• 分子量: 382.465
• InChiKey: PITUAFPHQAKRKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  91.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-氯-3-甲基-1,2,4-噻唑 、 1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl) phenyl)urea 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 生成 1-ethyl-3-(4-(7-(3-methyl-1,2,4-thiadiazol-5-yl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea
  参考文献：
  名称：

  [EN] PYRIMIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSÉS DE PYRIMIDINE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION

  摘要：

  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）。

  公开号：

  WO2010014939A1
• 作为产物：
  描述：

  2,4-二氯-5,6-二氢吡啶并[3,4-d]嘧啶-7-甲酸叔丁酯 在 四(三苯基膦)钯 、 potassium acetate 、 sodium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 4.25h， 生成 1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl) phenyl)urea
  参考文献：
  名称：

  Potent, Selective, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin Kinase Domain Exhibiting Single Agent Antiproliferative Activity

  摘要：

  Selective inhibitors of mammalian target of rapamycin (mTOR) kinase based upon saturated heterocycles fused to a pyrimidine core were designed and synthesized. Each series produced compounds with K-i < 10 nM for the mTOR kinase and >500-fold selectivity over closely related PI3 kinases. This potency translated into strong pathway inhibition, as measured by phosphorylation of mTOR substrate proteins and antiproliferative activity in cell lines with a constitutively active PI3K pathway. Two compounds exhibiting suitable mouse PK were profiled in in vivo tumor models and were shown to suppress mTORC1 and mTORC2 signaling for over 12 h when dosed orally. Both compounds were additionally shown to suppress tumor growth in vivo in a PC3 prostate cancer model over a 14 day study.

  DOI：

  10.1021/jm301389h

文献信息

• 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）。
• PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
  申请人：Lynch Rosemary

  公开号：US20120065202A1

  公开（公告）日：2012-03-15

  The invention relates to compounds of formula (I) wherein X, R 1 , R 2 , T, m, n, o have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及式(I)的化合物，其中X，R1，R2，T，m，n，o的含义如所述和权利要求所述。所述化合物可用作mTOR的抑制剂，用于治疗或预防mTOR相关疾病和疾病。本发明还涉及包括所述化合物的制药组合物，以及作为药物的使用和制备这些化合物。
• Pyrimidine derivatives as mTOR inhibitors
  申请人：Lynch Rosemary

  公开号：US08785457B2

  公开（公告）日：2014-07-22

  The invention relates to compounds of formula (I) wherein X, R1, R2, T, m, n, o have the meaning as cited in the description and the claims. The compounds of formula (I) are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及式(I)化合物，其中X、R1、R2、T、m、n、o的含义如所述描述和权利要求所述。式(I)化合物可用作mTOR的抑制剂，用于治疗或预防mTOR相关疾病和疾病。本发明还涉及包括所述化合物的制药组合物，以及作为药物的使用和制备。
• PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS
  申请人：CELLZOME LIMITED

  公开号：US20140296234A1

  公开（公告）日：2014-10-02

  The invention relates to compounds of formula (I) wherein X, R 1 , R 2 , T, m, n, o have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments.

  本发明涉及式(I)的化合物，其中X、R1、R2、T、m、n、o的含义如说明书和权利要求所述。所述化合物可用作mTOR的抑制剂，用于治疗或预防与mTOR相关的疾病和障碍。本发明还涉及包括所述化合物的制药组合物，以及作为药物的使用和制备这种化合物。