2-(2,4-dihydroxyphenyl)-6-iodo-3H-quinazolin-4-one | 929695-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-(2,4-dihydroxyphenyl)-6-iodo-3H-quinazolin-4-one
• CAS: 929695-95-4
• 化学式: C₁₄H₉IN₂O₃
• 分子量: 380.142
• InChiKey: YLINVTWHWIOHEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  81.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,4-dihydroxyphenyl)-6-iodo-3H-quinazolin-4-one 生成 tetraammonium 2-(2',4'-diphosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone
  参考文献：
  名称：

  Molecular-Docking-Guided Design, Synthesis, and Biologic Evaluation of Radioiodinated Quinazolinone Prodrugs

  摘要：

  Enzyme-mediated cancer imaging and therapy (EMCIT) is a novel approach in which radioactive water-soluble molecules are precipitated in vivo following their hydrolysis by extracellular enzymes overexpressed by cancer cells. AutoDock 3.0 was used to model the interaction-binding between a series of iodinated quinazolinone derivatives and human placental alkaline phosphatase (PLAP, crystal structure in the Protein Data Bank) and to assess the effects of structural modification of the derivatives. Ammonium 2-(2',4'-diphosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ(2-P,4-P)), having the most favorable calculated inhibition constant, was synthesized and characterized. Concentration-dependent, PLAP-mediated conversion of IQ(2-P,4-P) (4)/(125)IQ(2-P,4-P) (6) to water-insoluble 2-(2',4'-dihydroxyphenyl)-6-[I-127/I-125]iodo-4-(3H)-quinazolinone ((127)IQ(2-OH,4-OH) (2)/(125)IQ(2-OH,4-OH) (7)) was observed in solution. Autoradiography indicated that 6 is hydrolyzed by human cancer cells and the resulting 7 precipitates on exterior cell surfaces. Biodistribution studies in mice demonstrated that 6 is minimally retained by normal tissues. The findings support the validity of the EMCIT approach.

  DOI：

  10.1021/jm060944k
• 作为产物：
  描述：

  tetraammonium 2-(2',4'-diphosphoryloxyphenyl)-6-[127I]iodo-4-(3H)-quinazolinone 在 human placental alkaline phosphatase 、 tris-buffer 作用下， 生成 2-(2,4-dihydroxyphenyl)-6-iodo-3H-quinazolin-4-one
  参考文献：
  名称：

  Molecular-Docking-Guided Design, Synthesis, and Biologic Evaluation of Radioiodinated Quinazolinone Prodrugs

  摘要：

  Enzyme-mediated cancer imaging and therapy (EMCIT) is a novel approach in which radioactive water-soluble molecules are precipitated in vivo following their hydrolysis by extracellular enzymes overexpressed by cancer cells. AutoDock 3.0 was used to model the interaction-binding between a series of iodinated quinazolinone derivatives and human placental alkaline phosphatase (PLAP, crystal structure in the Protein Data Bank) and to assess the effects of structural modification of the derivatives. Ammonium 2-(2',4'-diphosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ(2-P,4-P)), having the most favorable calculated inhibition constant, was synthesized and characterized. Concentration-dependent, PLAP-mediated conversion of IQ(2-P,4-P) (4)/(125)IQ(2-P,4-P) (6) to water-insoluble 2-(2',4'-dihydroxyphenyl)-6-[I-127/I-125]iodo-4-(3H)-quinazolinone ((127)IQ(2-OH,4-OH) (2)/(125)IQ(2-OH,4-OH) (7)) was observed in solution. Autoradiography indicated that 6 is hydrolyzed by human cancer cells and the resulting 7 precipitates on exterior cell surfaces. Biodistribution studies in mice demonstrated that 6 is minimally retained by normal tissues. The findings support the validity of the EMCIT approach.

  DOI：

  10.1021/jm060944k