(S)-1-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-3-(3-(dimethylamino)propyl)urea

• 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: (S)-1-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-3-(3-(dimethylamino)propyl)urea
• 英文别名: 1-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-3-[3-(dimethylamino)propyl]urea
• 化学式: C₂₄H₂₈ClFN₆O₃
• 分子量: 502.976
• InChiKey: AMQVRRBXYZICIR-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-氯-N-(3-氯-4-氟苯基)-6-硝基-4-氨基喹唑啉 在 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (S)-1-(4-(3-chloro-4-fluorophenylamino)-7-(tetrahydrofuran-3-yloxy)quinazolin-6-yl)-3-(3-(dimethylamino)propyl)urea
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor

  摘要：

  A novel series of anilinoquinazoline compounds with C-6 urea-linked side chains was designed and synthesized as reversible inhibitors of epidermal growth factor receptor (EGFR) based on the structure-activity relationships (SARs) of anilinoquinazoline inhibitors. All compounds demonstrated good inhibition of EGFR wild type (EGFR wt) (IC50 = 0.024-1.715 mu M) and inhibited proliferation of A431cell line (IC50 = 0.116-22.008 mu M). The binding mode of compounds 8a, 8d, 8k and 8o was consistent with the biological results. Moreover, compounds 8k and 8l almost completely blocked the phosphorylation of EGFR in A431 cell line at 0.01 mu M. Interestingly, all of the compounds also demonstrated moderate inhibition of EGFR/T790M/L858R (IC50 = 0.049-5.578 mu M). In addition, compounds 8f and 8h blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (10 mu M), and compound 8f was confirmed to be an irreversible inhibitor through the dilution method. Importantly, the compounds with C-6 urea-linked side chains which did not contain Michael acceptors demonstrated moderate to strong irreversible EGFR inhibition. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.09.049

文献信息

• Design, synthesis and biological evaluation of novel 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of the epidermal growth factor receptor
  作者：Xu Zhang、Ting Peng、Xun Ji、Jian Li、Linjiang Tong、Zeng Li、Wei Yang、Yungen Xu、Mengyuan Li、Jian Ding、Hualiang Jiang、Hua Xie、Hong Liu

  DOI：10.1016/j.bmc.2013.09.049

  日期：2013.12

  A novel series of anilinoquinazoline compounds with C-6 urea-linked side chains was designed and synthesized as reversible inhibitors of epidermal growth factor receptor (EGFR) based on the structure-activity relationships (SARs) of anilinoquinazoline inhibitors. All compounds demonstrated good inhibition of EGFR wild type (EGFR wt) (IC50 = 0.024-1.715 mu M) and inhibited proliferation of A431cell line (IC50 = 0.116-22.008 mu M). The binding mode of compounds 8a, 8d, 8k and 8o was consistent with the biological results. Moreover, compounds 8k and 8l almost completely blocked the phosphorylation of EGFR in A431 cell line at 0.01 mu M. Interestingly, all of the compounds also demonstrated moderate inhibition of EGFR/T790M/L858R (IC50 = 0.049-5.578 mu M). In addition, compounds 8f and 8h blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (10 mu M), and compound 8f was confirmed to be an irreversible inhibitor through the dilution method. Importantly, the compounds with C-6 urea-linked side chains which did not contain Michael acceptors demonstrated moderate to strong irreversible EGFR inhibition. (C) 2013 Published by Elsevier Ltd.