2-氰基-3-((3-乙氧基苯基)氨基)丙烯酸乙酯 | 909513-02-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-氰基-3-((3-乙氧基苯基)氨基)丙烯酸乙酯
• 中文别名: 2-氰基-3 - ((3-乙氧基苯基)氨基)丙烯酸乙酯
• 英文名称: Ethyl 2-Cyano-3-((3-ethoxyphenyl)amino)acrylate
• 英文别名: ethyl (E)-2-cyano-3-(3-ethoxyanilino)prop-2-enoate
• CAS: 909513-02-6
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: WQWZWFBTQHDMFZ-ZHACJKMWSA-N

物化性质

• 沸点：
  391.3±42.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氰基-3-((3-乙氧基苯基)氨基)丙烯酸乙酯 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 甲醇 、 异丙醇 为溶剂， 反应 12.25h， 生成 培利替尼
  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
• 作为产物：
  描述：

  2-cyano-3-ethoxyacrylic acid ethyl ester 、 间氨基苯乙醚 以 甲苯 为溶剂， 反应 16.0h， 生成 2-氰基-3-((3-乙氧基苯基)氨基)丙烯酸乙酯
  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