[5-(1-Methylpiperidin-4-yl)oxy-4-oxo-7-phenylmethoxyquinazolin-3-yl]methyl 2,2-dimethylpropanoate | 525593-07-1

• 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: [5-(1-Methylpiperidin-4-yl)oxy-4-oxo-7-phenylmethoxyquinazolin-3-yl]methyl 2,2-dimethylpropanoate
• CAS: 525593-07-1
• 化学式: C₂₇H₃₃N₃O₅
• 分子量: 479.576
• InChiKey: BUBRSJHBHPNAJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  80.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-(1-Methylpiperidin-4-yl)oxy-4-oxo-7-phenylmethoxyquinazolin-3-yl]methyl 2,2-dimethylpropanoate 在 盐酸 、 四氯化碳 、 氨 、 三苯基膦 、 三氟乙酸 作用下， 以 甲醇 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 8.5h， 生成 4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-5-[(1-methylpiperidin-4-yl)oxy]quinazolin-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
• 作为产物：
  描述：

  1-甲基-4-哌啶醇 、 (7-(benzyloxy)-5-hydroxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 [5-(1-Methylpiperidin-4-yl)oxy-4-oxo-7-phenylmethoxyquinazolin-3-yl]methyl 2,2-dimethylpropanoate
  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

文献信息

• Quinazoline derivatives as antitumor agents
  申请人：Hennequin Francois Andre Laurent

  公开号：US20050054662A1

  公开（公告）日：2005-03-10

  The invention concerns quinazoline derivatives of Formula (I); wherein each of Q 1 , Q 2 , Z, R 1 , R 2 , R 3 , and m have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosin kinases.

  该发明涉及公式（I）的喹唑啉衍生物；其中Q1、Q2、Z、R1、R2、R3和m中的每一个都具有描述中定义的任何含义；它们的制备过程，包含它们的制药组合物以及它们在制造对erbB受体酪氨酸激酶抑制敏感的肿瘤的预防或治疗药物中的使用。
• QUINAZOLINE DERIVATIVES AS ANTITUMOR AGENTS
  申请人：AstraZeneca AB

  公开号：EP1444211A2

  公开（公告）日：2004-08-11
• EP1444211B1
  申请人：——

  公开号：EP1444211B1

  公开（公告）日：2009-01-21
• [EN] QUINAZOLINE DERIVATIVES AS ANTITUMOR AGENTS<br/>[FR] DERIVES DE LA QUINAZOLINE, AGENTS ANTI-TUMORAUX
  申请人：ASTRAZENECA AB

  公开号：WO2003040109A2

  公开（公告）日：2003-05-15

  The invention concerns quinazoline derivatives of Formula (I); wherein each of Q?1, Q2, Z, R1, R2, R3¿, L and m have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.