4-(2-morpholino-6-(quinolin-3-ylamino)pyrimidin-4-yl)pyridin-2-ol | 1262950-31-1

• 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: 4-(2-morpholino-6-(quinolin-3-ylamino)pyrimidin-4-yl)pyridin-2-ol
• 英文别名: 2-Morpholino-6-(quinolin-3-ylamino)-4,5''-bipyrimidin-2''-ol；5-[2-morpholin-4-yl-6-(quinolin-3-ylamino)pyrimidin-4-yl]-1H-pyrimidin-2-one
• CAS: 1262950-31-1
• 化学式: C₂₁H₁₉N₇O₂
• 分子量: 401.428
• InChiKey: PIIRYJPFVYQGQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 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：
  105
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(6-bromo-2-morpholinopyrimidin-4-yl)quinolin-3-amine 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 为溶剂， 反应 15.17h， 生成 4-(2-morpholino-6-(quinolin-3-ylamino)pyrimidin-4-yl)pyridin-2-ol
  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.