N-[3-[[5-chloro-2-[2-methoxyl-4-(1H-imidazol-1-ylmethyl)phenylamino]-4-pyrimidinyl]amino]phenyl]-2-propenamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-[[5-chloro-2-[2-methoxyl-4-(1H-imidazol-1-ylmethyl)phenylamino]-4-pyrimidinyl]amino]phenyl]-2-propenamide
• 英文别名: N-[3-[[5-chloro-2-[[4-((1H-imidazol-1-yl))methyl-2-methoxyphenyl]amino]-4-pyrimidinyl]amino]phenyl]-2-propenamide；N-[3-[[5-chloro-2-[4-(imidazol-1-ylmethyl)-2-methoxyanilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide
• 化学式: C₂₄H₂₂ClN₇O₂
• 分子量: 475.937
• InChiKey: WBNROVQHGIUYRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-溴甲基-2-甲氧基-1-硝基苯 在 铁粉 、 potassium carbonate 、 氯化铵 、 三氟乙酸 作用下， 以 甲醇 、 水 、 乙腈 、 仲丁醇 为溶剂， 反应 7.0h， 生成 N-[3-[[5-chloro-2-[2-methoxyl-4-(1H-imidazol-1-ylmethyl)phenylamino]-4-pyrimidinyl]amino]phenyl]-2-propenamide
  参考文献：
  名称：

  Synthesis and biological evaluation of azole-diphenylpyrimidine derivatives (AzDPPYs) as potent T790M mutant form of epidermal growth factor receptor inhibitors

  摘要：

  A series of novel azole-diphenylpyrimidine derivatives (AzDPPYs) were synthesized and biologically evaluated as potent EGFR(T790M) inhibitors. Among these analogues, the most active inhibitor 6e not only displayed high activity against EGFR(T790M/L858R) kinase (IC50 = 33 nM), but also was able to repress the replication of H1975 cells harboring EGFR(T790M) mutation at a concentration of 0.118 mu mol/L. In contrast to the lead compound rociletinib, 6e slightly reduces the key EGFRT790M-minduced drug resistance. Significantly, inhibitor 6e demonstrates high selectivity (SI = 299.3) for T790M-containing EGFR mutants over wild type EGFR, hinting that it will cause less side effects. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.001

文献信息

• Synthesis and biological evaluation of azole-diphenylpyrimidine derivatives (AzDPPYs) as potent T790M mutant form of epidermal growth factor receptor inhibitors
  作者：Zhendong Song、Yue Jin、Yang Ge、Changyuan Wang、Jianbin Zhang、Zeyao Tang、Jinyong Peng、Kexin Liu、Yanxia Li、Xiaodong Ma

  DOI：10.1016/j.bmc.2016.09.001

  日期：2016.11

  A series of novel azole-diphenylpyrimidine derivatives (AzDPPYs) were synthesized and biologically evaluated as potent EGFR(T790M) inhibitors. Among these analogues, the most active inhibitor 6e not only displayed high activity against EGFR(T790M/L858R) kinase (IC50 = 33 nM), but also was able to repress the replication of H1975 cells harboring EGFR(T790M) mutation at a concentration of 0.118 mu mol/L. In contrast to the lead compound rociletinib, 6e slightly reduces the key EGFRT790M-minduced drug resistance. Significantly, inhibitor 6e demonstrates high selectivity (SI = 299.3) for T790M-containing EGFR mutants over wild type EGFR, hinting that it will cause less side effects. (C) 2016 Elsevier Ltd. All rights reserved.