(E)-3-(4-chlorophenyl)-1-{4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl}prop-2-en-1-one | 1582283-84-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(4-chlorophenyl)-1-{4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl}prop-2-en-1-one
• 英文别名: HER2/EGFR dual kinase inhibitor, 7e；(E)-3-(4-chlorophenyl)-1-[4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]prop-2-en-1-one
• CAS: 1582283-84-8
• 化学式: C₂₅H₂₀ClN₃O₃
• 分子量: 445.905
• InChiKey: MIFKLWONDMFKNY-LFYBBSHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-chlorophenyl)-1-{4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl}prop-2-en-1-one 、 溶剂黄146 在 一水合肼 作用下， 反应 5.0h， 生成
  参考文献：
  名称：

  Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents

  摘要：

  Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 40 position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 mu M, respectively, and with IC50 equal to 3.98 and 1.04 mu M on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 mu M, respectively.

  DOI：

  10.3109/14756366.2013.765417
• 作为产物：
  描述：

  4-氯-6,7-二甲氧基喹唑啉 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 5.0h， 生成 (E)-3-(4-chlorophenyl)-1-{4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl}prop-2-en-1-one
  参考文献：
  名称：

  Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents

  摘要：

  Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 40 position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 mu M, respectively, and with IC50 equal to 3.98 and 1.04 mu M on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 mu M, respectively.

  DOI：

  10.3109/14756366.2013.765417

文献信息

• Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents
  作者：Maiada M. Sadek、Rabah A. Serrya、Abdel-Hamid N. Kafafy、Marawan Ahmed、Feng Wang、Khaled A. M. Abouzid

  DOI：10.3109/14756366.2013.765417

  日期：2014.4.1

  Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 40 position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 mu M, respectively, and with IC50 equal to 3.98 and 1.04 mu M on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 mu M, respectively.