6-bromo-2-morpholino-N-(6-phenoxypyridin-3-yl)pyrimidin-4-amine | 1254697-47-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-bromo-2-morpholino-N-(6-phenoxypyridin-3-yl)pyrimidin-4-amine
• CAS: 1254697-47-6
• 化学式: C₁₉H₁₈BrN₅O₂
• 分子量: 428.288
• InChiKey: CGOHFJLMMPAUEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  72.4
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-氨基嘧啶-5-硼酸频哪酯 、 6-bromo-2-morpholino-N-(6-phenoxypyridin-3-yl)pyrimidin-4-amine 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.17h， 生成 2-morpholino-N6-(6-phenoxypyridin-3-yl)-4,5'-bipyrimidine-2',6-diamine
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors

  摘要：

  Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. series of 2 morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure guided optimization of these,pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered,Within-this series a compound, 17, Was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKT(Ser473) phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

  DOI：

  10.1021/ml1001932
• 作为产物：
  描述：

  吗啉 、 2,4,6-三溴嘧啶 、 6-苯氧基-3-吡啶胺 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 6-bromo-2-morpholino-N-(6-phenoxypyridin-3-yl)pyrimidin-4-amine
  参考文献：
  名称：

  Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors

  摘要：

  Phospoinositide-3-kinases (PI3K) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. series of 2 morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure guided optimization of these,pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered,Within-this series a compound, 17, Was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKT(Ser473) phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

  DOI：

  10.1021/ml1001932