[4-[3-Chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-[5-[(4-hydroxybutylamino)methyl]furan-2-yl]-2-(sulfomethyl)quinazolin-5-yl]methanesulfonic acid

• 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-[3-Chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-[5-[(4-hydroxybutylamino)methyl]furan-2-yl]-2-(sulfomethyl)quinazolin-5-yl]methanesulfonic acid
• 英文别名: [4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-[5-[(4-hydroxybutylamino)methyl]furan-2-yl]-2-(sulfomethyl)quinazolin-5-yl]methanesulfonic acid
• 化学式: C₃₂H₃₂ClFN₄O₉S₂
• 分子量: 735.2
• InChiKey: YDSUISIUBNHBLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  218
• 氢给体数：
  5
• 氢受体数：
  14

文献信息

• QUINAZOLINE DERIVATIVE, COMPOSITION HAVING THE DERIVATIVE, AND USE OF THE DERIVATIVE IN PREPARING MEDICAMENT
  申请人：Hangzhou Minsheng Institutes for Pharma Research

  公开号：EP2740729A1

  公开（公告）日：2014-06-11

  A class of quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof with novel structures is provided; meanwhile, a pharmaceutical composition comprising a pharmaceutically effective amountof said quinazoline derivatives or pharmaceutically acceptable salts or solvates thereof, and pharmaceutically acceptable excipients or additives is also provided. By modifying and transforming the quinazoline and screening of the transformed compounds on the activity of tyrosine kinase inhibition, most of the compounds have been found to possess inhibitory activity against one or several of EGFR, VEGFR-2, c-erbB-2, c-erbB-4, c-met, tie-2, PDGFR, c-src, lck, Zap70 and fyn kinases. The present invention has the advantages of reasonable design, broad source of and easy access to the raw materials, simple and easy operation of the preparation methods, mild reaction conditions, high yield of the products and being beneficial for industrial-scale production.

  本研究提供了一类结构新颖的喹唑啉衍生物或其药学上可接受的盐或溶剂；同时，还提供了一种药物组合物，该药物组合物包含药学上有效量的上述喹唑啉衍生物或其药学上可接受的盐或溶剂，以及药学上可接受的赋形剂或添加剂。通过对喹唑啉进行修饰和转化，并对转化后的化合物进行酪氨酸激酶抑制活性筛选，发现大多数化合物对表皮生长因子受体（EGFR）、血管内皮生长因子受体（VEGFR-2）、c-erbB-2、c-erbB-4、c-met、tie-2、PDGFR、c-src、lck、Zap70 和 fyn 激酶中的一种或几种具有抑制活性。本发明具有设计合理、原料来源广且易得、制备方法简单易操作、反应条件温和、产物收率高、有利于工业化生产等优点。