N-(6-(5-aminopyrazin-2-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-amine | 1254697-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(6-(5-aminopyrazin-2-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-amine
• 英文别名: N-[6-(5-aminopyrazin-2-yl)-2-morpholin-4-ylpyrimidin-4-yl]quinolin-3-amine
• CAS: 1254697-40-9
• 化学式: C₂₁H₂₀N₈O
• 分子量: 400.443
• InChiKey: GTSVWFMEUUHFOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(6-bromo-2-morpholinopyrimidin-4-yl)quinolin-3-amine 、 5-氨基吡嗪-2-硼酸频那醇酯 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 N-(6-(5-aminopyrazin-2-yl)-2-morpholinopyrimidin-4-yl)quinolin-3-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