N2'-methyl-2-morpholino-N6-(quinolin-3-yl)-4,5'-bipyrimidine-2',6-diamine | 1254697-44-3

• 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: N2'-methyl-2-morpholino-N6-(quinolin-3-yl)-4,5'-bipyrimidine-2',6-diamine
• 英文别名: N-[6-[2-(methylamino)pyrimidin-5-yl]-2-morpholin-4-ylpyrimidin-4-yl]quinolin-3-amine
• CAS: 1254697-44-3
• 化学式: C₂₂H₂₂N₈O
• 分子量: 414.47
• InChiKey: JIPRSFBAFUWPLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  5-溴-2-甲基氨基嘧啶 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 为溶剂， 反应 4.17h， 生成 N2'-methyl-2-morpholino-N6-(quinolin-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

文献信息

• Synthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors
  作者：Matthew T. Burger、Mark Knapp、Allan Wagman、Zhi-Jie Ni、Thomas Hendrickson、Gordana Atallah、Yanchen Zhang、Kelly Frazier、Joelle Verhagen、Keith Pfister、Simon Ng、Aaron Smith、Sarah Bartulis、Hanne Merrit、Marion Weismann、Xiaohua Xin、Joshua Haznedar、Charles F. Voliva、Ed Iwanowicz、Sabina Pecchi

  DOI：10.1021/ml1001932

  日期：2011.1.13

  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.