2-(4-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidine | 1542142-10-8

• 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: 2-(4-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidine
• 英文别名: 4-(4-Morpholin-4-ylpyrido[3,2-d]pyrimidin-2-yl)aniline；4-(4-morpholin-4-ylpyrido[3,2-d]pyrimidin-2-yl)aniline
• CAS: 1542142-10-8
• 化学式: C₁₇H₁₇N₅O
• 分子量: 307.355
• InChiKey: MFXSRQDXRUJPEB-UHFFFAOYSA-N

物化性质

• 熔点：
  221-223 °C
• 沸点：
  469.6±45.0 °C(predicted)
• 密度：
  1.312±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  三光气 、 对氨基苯甲醇 、 2-(4-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidine 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.75h， 生成 2-(4-(1-(4-(hydroxymethyl)phenyl)-3-phenylurea))-4-morpholinopyrido[3,2-d]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Pyridopyrimidine Scaffolds as Novel PI3K/mTOR Dual Inhibitors

  摘要：

  The design, synthesis, and screening of dual PI3K/mTOR inhibitors that gave nanomolar enzymatic and cellular activities on both targets with an acceptable kinase selectivity profile are described. A docking study was performed to understand the binding mode of the compounds and to explain the differences in biological activity. In addition, cellular effects of the best dual inhibitors were determined on six cancer cell lines and compared to those on a healthy diploid cell line for cellular cytotoxicity. Two compounds are highly potent on cancer cells in the submicromolar range without any toxicity on healthy cells. A more detailed analysis of the cellular effect of these PI3K/mTOR dual inhibitors demonstrated that they induce GI-phase cell cycle arrest in breast cancer cells and trigger apoptosis. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds or as a chemical series for further optimization to progress into in vivo experiments.

  DOI：

  10.1021/jm401138v
• 作为产物：
  描述：

  4-(2-(4-nitrophenyl)pyrido[3,2-d]pyrimidin-4-yl)morpholine 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以80%的产率得到2-(4-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidine
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Pyridopyrimidine Scaffolds as Novel PI3K/mTOR Dual Inhibitors

  摘要：

  The design, synthesis, and screening of dual PI3K/mTOR inhibitors that gave nanomolar enzymatic and cellular activities on both targets with an acceptable kinase selectivity profile are described. A docking study was performed to understand the binding mode of the compounds and to explain the differences in biological activity. In addition, cellular effects of the best dual inhibitors were determined on six cancer cell lines and compared to those on a healthy diploid cell line for cellular cytotoxicity. Two compounds are highly potent on cancer cells in the submicromolar range without any toxicity on healthy cells. A more detailed analysis of the cellular effect of these PI3K/mTOR dual inhibitors demonstrated that they induce GI-phase cell cycle arrest in breast cancer cells and trigger apoptosis. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds or as a chemical series for further optimization to progress into in vivo experiments.

  DOI：

  10.1021/jm401138v

文献信息

• Design, Synthesis, and Biological Activity of Pyridopyrimidine Scaffolds as Novel PI3K/mTOR Dual Inhibitors
  作者：Thibault Saurat、Frédéric Buron、Nuno Rodrigues、Marie-Ludivine de Tauzia、Lionel Colliandre、Stéphane Bourg、Pascal Bonnet、Gérald Guillaumet、Mohamed Akssira、Anne Corlu、Christiane Guillouzo、Pauline Berthier、Pascale Rio、Marie-Lise Jourdan、Hélène Bénédetti、Sylvain Routier

  DOI：10.1021/jm401138v

  日期：2014.2.13

  The design, synthesis, and screening of dual PI3K/mTOR inhibitors that gave nanomolar enzymatic and cellular activities on both targets with an acceptable kinase selectivity profile are described. A docking study was performed to understand the binding mode of the compounds and to explain the differences in biological activity. In addition, cellular effects of the best dual inhibitors were determined on six cancer cell lines and compared to those on a healthy diploid cell line for cellular cytotoxicity. Two compounds are highly potent on cancer cells in the submicromolar range without any toxicity on healthy cells. A more detailed analysis of the cellular effect of these PI3K/mTOR dual inhibitors demonstrated that they induce GI-phase cell cycle arrest in breast cancer cells and trigger apoptosis. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds or as a chemical series for further optimization to progress into in vivo experiments.