2-(3-methoxy-5-methylphenyl)-4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidine | 1509920-02-8

• 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-(3-methoxy-5-methylphenyl)-4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidine
• CAS: 1509920-02-8
• 化学式: C₂₁H₂₀N₄O₃
• 分子量: 376.415
• InChiKey: WXPSAYDJMFOFIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  28.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  73.51
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-(3-methoxy-5-methylphenyl)-4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidine 在 水 、 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 48.0h， 以45.7%的产率得到3-methyl-5-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
  参考文献：
  名称：

  Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design

  摘要：

  The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3K alpha-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R-1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3K alpha-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3K alpha inhibitors.

  DOI：

  10.1021/ml400378e
• 作为产物：
  描述：

  3-氨基-呋喃并[2,3-B]嘧啶-2-甲酸乙酯 在 吡啶 、 ammonium hydroxide 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 18.0h， 生成 2-(3-methoxy-5-methylphenyl)-4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidine
  参考文献：
  名称：

  Crystal Structures of PI3Kα Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design

  摘要：

  The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3K alpha-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R-1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3K alpha-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3K alpha inhibitors.

  DOI：

  10.1021/ml400378e