N-(3-((2-((4-methoxyphenyl)amino)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-yl)oxy)phenyl)acrylamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃吡啶类
• 英文名称: N-(3-((2-((4-methoxyphenyl)amino)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-yl)oxy)phenyl)acrylamide
• 英文别名: Egfr-IN-56；N-[3-[[2-(4-methoxyanilino)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide
• 化学式: C₂₃H₂₂N₄O₃S
• 分子量: 434.519
• InChiKey: MXQIWUCOUMEFAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1,5,7,8‐tetrahydro‐2H‐thiopyrano[4,3‐d]pyrimidine‐2,4(3H)‐dione 在 iron(III) chloride hexahydrate 、 sodium methylate 、 甲烷 、 caesium carbonate 、 对甲苯磺酸 、 一水合肼 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.0h， 生成 N-(3-((2-((4-methoxyphenyl)amino)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-yl)oxy)phenyl)acrylamide
  参考文献：
  名称：

  Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors

  摘要：

  A series of novel thiapyran-pyrimidine derivatives (10a-10h, 11a-11g, 12a-12f, 13a-13f, 14a-14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFR(T790M/L858R) in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure-activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.

  DOI：

  10.1016/j.bmc.2020.115669

文献信息

• Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors
  作者：Zhen Xiao、Cilong Chu、Lingjia Zhou、Zhihui Zhou、Qian Zhang、Feiyi Yang、Zunhua Yang、Pengwu Zheng、Shan Xu、Wufu Zhu

  DOI：10.1016/j.bmc.2020.115669

  日期：2020.10

  A series of novel thiapyran-pyrimidine derivatives (10a-10h, 11a-11g, 12a-12f, 13a-13f, 14a-14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFR(T790M/L858R) in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure-activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.