ethyl 3-(3-methoxy-5-nitrobenzamido)furo[2,3-b]pyridine-2-carboxylate | 1509919-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-(3-methoxy-5-nitrobenzamido)furo[2,3-b]pyridine-2-carboxylate
• CAS: 1509919-80-5
• 化学式: C₁₈H₁₅N₃O₇
• 分子量: 385.333
• InChiKey: BFWVQSPVPPIZTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  133.8
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-methoxy-5-nitrobenzamido)furo[2,3-b]pyridine-2-carboxylate 在 ammonium hydroxide 、 氯化亚砜 、 水 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 异丙醇 为溶剂， 反应 16.0h， 生成 2-(3-methoxy-5-nitrophenyl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-4(3H)-one
  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-甲氧基-5-硝基苯甲酸 在 吡啶 、 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 ethyl 3-(3-methoxy-5-nitrobenzamido)furo[2,3-b]pyridine-2-carboxylate
  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