4-(2-chloro-5-methoxyanilino)-7-methoxy-5-(3-morpholinopropoxy)quinazoline

• 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-(2-chloro-5-methoxyanilino)-7-methoxy-5-(3-morpholinopropoxy)quinazoline
• 英文别名: N-(2-chloro-5-methoxyphenyl)-7-methoxy-5-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
• 化学式: C₂₃H₂₇ClN₄O₄
• 分子量: 458.945
• InChiKey: NGTKKGNCMAPUNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氯-5,7-二甲氧基喹唑啉 在 吡啶 、 吡啶盐酸盐 、 三苯基膦 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 2.5h， 生成 4-(2-chloro-5-methoxyanilino)-7-methoxy-5-(3-morpholinopropoxy)quinazoline
  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 for treatment of tumours
  申请人：AstraZeneca AB

  公开号：US07049438B2

  公开（公告）日：2006-05-23

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, m, R1, R2, R3 and Q2 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 as an anti-invasive agent in the containment and/or treatment of solid tumour disease

  该发明涉及公式（I）的喹唑啉衍生物，其中Q1、Z、m、R1、R2、R3和Q2中的每一个都具有在说明书中定义的任何含义；制备它们的过程，包含它们的制药组合物以及它们在制造用于抗侵袭剂的药物治疗固体肿瘤疾病的药物中的使用。
• Quinazoline derivatives for the treatment of tumours
  申请人：AstraZeneca AB

  公开号：US07696214B2

  公开（公告）日：2010-04-13

  The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, m, R1, R2, R3 and Q2 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 as an anti-invasive agent in the containment and/or treatment of solid tumor disease.

  本发明涉及公式（I）的喹唑啉衍生物，其中Q1、Z、m、R1、R2、R3和Q2中的每一个都具有描述中定义的任何含义；制备它们的过程，包含它们的制药组合物以及它们在制造用于抗侵袭剂在固体肿瘤疾病的控制和/或治疗中使用的药物的制造中的用途。
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF TUMOURS
  申请人：AstraZeneca AB

  公开号：EP1292594B1

  公开（公告）日：2004-09-01
• QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF T CELL MEDIATED DISEASES
  申请人：Astrazeneca AB

  公开号：EP1450808B1

  公开（公告）日：2005-06-15
• US7049438B2
  申请人：——

  公开号：US7049438B2

  公开（公告）日：2006-05-23