4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-ol | 401810-85-3

• 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-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-ol
• 英文别名: 4-(6-chloro-2,3-methylenedioxyanilino)-7-hydroxy-6-methoxyquinazoline
• CAS: 401810-85-3
• 化学式: C₁₆H₁₂ClN₃O₄
• 分子量: 345.742
• InChiKey: JMZISWGTDQVVCI-UHFFFAOYSA-N

物化性质

• 沸点：
  489.8±45.0 °C(Predicted)
• 密度：
  1.560±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  85.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-羟甲基吡啶-2-腈 、 4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-ol 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到4-(6-chloro-2,3-methylenedioxyanilino)-7-(2-cyanopyrid-4-ylmethoxy)-6-methoxyquinazoline
  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
• 作为产物：
  描述：

  5-氯苯并[1,3]二恶茂-4-胺 在 盐酸 、 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 4.0h， 生成 4-[(5-chloro-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-ol
  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
  申请人：——

  公开号：US20040034046A1

  公开（公告）日：2004-02-19

  The invention concerns quinazoline derivatives of Formula (I) 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中用于抑制和/或治疗实体肿瘤疾病的用途。
• [EN] QUINAZOLINE DERIVATIVES<br/>[FR] DERIVES DE QUINAZOLINE
  申请人：ASTRAZENECA AB

  公开号：WO2002016352A1

  公开（公告）日：2002-02-28

  The invention concerns quinazoline derivatives of Formula (I) wherein each of m, R?1, n, R2 and R3¿ 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.

  本发明涉及式（I）的喹唑啉衍生物，其中m、R1、n、R2和R3中的每一个具有在说明书中定义的任何含义；它们的制备过程，包含它们的制药组合物以及它们在制造用于抗侵袭剂治疗和/或治疗实体瘤疾病的药物中的使用。
• Therapeutic use
  申请人：Moore Corine Nelly

  公开号：US20050014773A1

  公开（公告）日：2005-01-20

  The invention concerns the use of the quinazoline derivatives of Formula (I) Wherein each of m, R 1 , n, R 2 and R 3 have any of the meanings defined in the description in the manufacture of a medicament for use in the prevention or treatment of T cell mediated diseases or medical conditions such as autoimmune diseases like transplant rejection or rheumatoid arthritis in a warm-blooded animal.

  本发明涉及使用式（I）中的喹唑啉衍生物，在制备用于预防或治疗T细胞介导的疾病或医疗状况，例如自身免疫疾病，如移植排斥或类风湿性关节炎等热血动物的药物中，其中m，R1，n，R2和R3中的每一个具有描述中定义的任何含义。
• QUINAZOLINE DERIVATIVES
  申请人：AstraZeneca AB

  公开号：EP1313727A1

  公开（公告）日：2003-05-28
• USE OF QUINAZOLINES TO TREAT T-CELL MEDIATED DISEASES
  申请人：AstraZeneca AB

  公开号：EP1453492B1

  公开（公告）日：2007-01-24