N-(3-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

• 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: N-(3-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
• 化学式: C₂₄H₂₅ClN₄O₄
• 分子量: 468.94
• InChiKey: NARYDJIDKAGQQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-(3-羟丙基)吗啉 在 盐酸 、 氯化亚砜 、 氨 、 N,N-二甲基甲酰胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 4.5h， 生成 N-(3-chloro-1-benzofuran-7-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine
  参考文献：
  名称：

  Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src

  摘要：

  Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.

  DOI：

  10.1021/jm030317k

文献信息

• Quinazoline derivatives with anti-tumour activity
  申请人：AstraZeneca AB

  公开号：US20040048881A1

  公开（公告）日：2004-03-11

  The invention concerns quinazoline derivatives of Formula I 1 wherein each of m, R 1 , n, R 2 and R 3 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.

  这项发明涉及式I的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有描述中定义的任意含义；它们的制备方法，含有它们的药物组合物以及它们在制造用作抗侵袭剂的药物的过程中在固体肿瘤疾病的控制和/或治疗中的使用。
• Combination product of inhibitor of the src family of non-recetpor tyrosine kinases and gemcitabine
  申请人：Barge Alan

  公开号：US20060142297A1

  公开（公告）日：2006-06-29

  The invention concerns a combination comprising an inhibitor of Src kinase and the cytotoxic agent gemcitabine, a pharmaceutical composition comprising such a combination and its use in the treatment or prophylaxis of cancer, particularly of pancreatic cancer.

  本发明涉及一种组合物，包括Src激酶抑制剂和细胞毒素吉西他滨，一种含有该组合物的药物组合物以及其在治疗或预防癌症，特别是胰腺癌方面的用途。
• QUINAZOLINE DERIVATIVES WITH ANTI-TUMOUR ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1326859A1

  公开（公告）日：2003-07-16
• COMBINATION PRODUCT OF INHIBITOR OF THE SRC FAMILY OF NON-RECEPTOR TYROSINE KINASES AND GEMCITABINE FOR USE IN THE TREATMENT OR PROPHLAXIX OF PANCREATIC CANCER
  申请人：AstraZeneca AB

  公开号：EP1562612B1

  公开（公告）日：2010-01-27
• US6849625B2
  申请人：——

  公开号：US6849625B2

  公开（公告）日：2005-02-01