4-trimethylammonium-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl]amide iodide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-trimethylammonium-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl]amide iodide
• 英文别名: [(E)-4-[[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]amino]-4-oxobut-2-enyl]-trimethylazanium;iodide
• 化学式: C₂₅H₂₆ClFN₅O₂*I
• 分子量: 609.87
• InChiKey: YARCNNNNPBYNOG-UHDJGPCESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  87
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  间氨基苯乙醚 在 N-甲基吡咯烷酮 、 diphenyl ether-biphenyl eutectic 、 亚硝酸铵 、 铁粉 、 氯化铵 、 三氟乙酸酐 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 、 甲苯 为溶剂， 反应 28.25h， 生成 4-trimethylammonium-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl]amide iodide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 6,7-Disubstituted 4-Anilinoquinoline-3-carbonitriles. The Design of an Orally Active, Irreversible Inhibitor of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (EGFR) and the Human Epidermal Growth Factor Receptor-2 (HER-2)

  摘要：

  A series of of 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER-2 kinases have been prepared. These inhibitors have, at the 6-position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(arylamino)quinoline-3-carbonitriles with unsaturated acid chlorides or mixed anhydrides. We performed competitive reactivity studies showing that attaching a dialkylamino group onto the end of the Michael acceptor results in compounds with greater reactivity due to intramolecular catalysis of the Michael addition. This, along with improved water-solubility results in compounds with enhanced biological properties. We present molecular modeling results consistent with the proposed mechanism of inhibition. One compound, 5 (EKB-569), which shows excellent oral in vivo activity, was selected for further studies and is currently in phase I clinical trials for the treatment of cancer.

  DOI：

  10.1021/jm020241c