6-氟-2,3-亚甲二氧基苯甲酸甲酯 | 492444-07-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 6-氟-2,3-亚甲二氧基苯甲酸甲酯
• 英文名称: methyl 5-fluoro-1,3-benzodioxole-4-carboxylate
• 英文别名: methyl 5-fluoro-2H-1,3-benzodioxolane-4-carboxylate；methyl 5-fluorobenzo[d][1,3]dioxole-4-carboxylate；1,3-Benzodioxole-4-carboxylicacid, 5-fluoro-, methyl ester
• CAS: 492444-07-2
• 化学式: C₉H₇FO₄
• 分子量: 198.151
• InChiKey: ITECBLQJGWNBRZ-UHFFFAOYSA-N

物化性质

• 沸点：
  290.9±40.0 °C(Predicted)
• 密度：
  1.388±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-氟-2,3-亚甲二氧基苯甲酸甲酯 在 盐酸 、 氢氧化钾 、 叠氮磷酸二苯酯 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 12.5h， 生成 N-(5-fluoro-1,3-benzodioxol-4-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
• 作为产物：
  描述：

  6-氟-2.3-二羟基苯甲酸 在 氯化亚砜 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 6-氟-2,3-亚甲二氧基苯甲酸甲酯
  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

• Quinoline derivatives and their use as tyrosine kinase inhibitors
  申请人：Hennequin Francois Andre Laurent

  公开号：US20050009867A1

  公开（公告）日：2005-01-13

  The invention concerns quinoline derivatives of Formula (I) wherein each of Z, m, R 1 , n 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.

  本发明涉及公式（I）的喹啉衍生物，其中Z，m，R1，n和R3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，含有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剂中的用途。
• QUINOLINE DERIVATIVES AND THEIR USE AS TYROSINE KINASE INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1409481B1

  公开（公告）日：2006-10-04
• US7501516B2
  申请人：——

  公开号：US7501516B2

  公开（公告）日：2009-03-10
• [EN] QUINOLINE DERIVATIVES AS ANTITUMOUR AGENTS<br/>[FR] DERIVES DE LA QUINOLEINE, UTILISES EN TANT QU'AGENTS ANTITUMORAUX
  申请人：ASTRAZENECA AB

  公开号：WO2003047582A1

  公开（公告）日：2003-06-12

  The invention concerns quinoline derivatives of Formula (I), wherein each of Z, m, R1, n 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.
• WO2024095005A1
  申请人：——

  公开号：——

  公开（公告）日：——