4-[(5-fluoro-1,3-benzodioxol-4-yl)amino]-5-isopropoxyquinazolin-7-ol | 914456-32-9

• 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: 4-[(5-fluoro-1,3-benzodioxol-4-yl)amino]-5-isopropoxyquinazolin-7-ol
• 英文别名: 4-[(5-Fluoro-1,3-benzodioxol-4-yl)amino]-5-propan-2-yloxyquinazolin-7-ol
• CAS: 914456-32-9
• 化学式: C₁₈H₁₆FN₃O₄
• 分子量: 357.341
• InChiKey: BRGVCCWYCZADIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  85.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[(5-fluoro-1,3-benzodioxol-4-yl)amino]-5-isopropoxyquinazolin-7-ol 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 1-{4-[2-({4-[(5-fluoro-2H-1,3-benzodioxol-4-yl)amino]-5-(propan-2-yloxy)quinazolin-7-yl}oxy)ethyl]piperazin-1-yl}ethan-1-one
  参考文献：
  名称：

  N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

  摘要：

  Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

  DOI：

  10.1021/jm060434q
• 作为产物：
  描述：

  7-(benzyloxy)-5-isopropoxyquinazolin-4(3H)-one 在 palladium on activated charcoal 吡啶 、 氨 、 ammonium formate 、 三氯氧磷 作用下， 以 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 7.0h， 生成 4-[(5-fluoro-1,3-benzodioxol-4-yl)amino]-5-isopropoxyquinazolin-7-ol
  参考文献：
  名称：

  N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

  摘要：

  Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

  DOI：

  10.1021/jm060434q