4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-[3-(3,4-dimethoxycinnamamido)phenoxy]pyrimidine

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-[3-(3,4-dimethoxycinnamamido)phenoxy]pyrimidine
• 英文别名: (E)-N-[3-[6-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]pyrimidin-4-yl]oxyphenyl]-3-(3,4-dimethoxyphenyl)prop-2-enamide
• 化学式: C₃₄H₂₈ClFN₄O₅
• 分子量: 627.072
• InChiKey: LIPSIDLSBZXGTC-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-硝基苯酚钠盐 在 盐酸 、 铁粉 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 8.0h， 生成 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-[3-(3,4-dimethoxycinnamamido)phenoxy]pyrimidine
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidines as dual EGFR/ErbB-2 kinase inhibitors

  摘要：

  A series of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidine derivatives were elaborately designed based on the skeleton of Lapatinib, and evaluated for their potential to inhibit epidermal growth factor receptor (EGFR) and ErbB-2 tyrosine kinase activities and antiproliferative activities against A431 and SKOV-3 cell lines. Among these synthesized pyrimidine derivatives, 4-[3-chloro-4-(3-fluorob enzyloxy)anilino]-6-(3-acrylamidophenoxy)pyrimidine (6), 4-13-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3cyanoacetamidophenoxy)pyrimidine (9), 4-[3-chloro-4-(3-fluorobenzyloxy)anilino)-6-(3-[6-(4-amino)pyri midinyl]amino) phenoxy)pyrimidine (11) and 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-phenoxyacetamidophenoxy)pyrimidine (14) could significantly inhibit dual EGFR/ErbB-2 kinase activities (IC50 = 37/29 nM, 48/38 nM, 61/42 nM, 65/79 nM, respectively). And compounds 6 and 11 also showed the most potent antiproliferative activities in vitro, with the IC50 value of 6 being 3.25 mu M for A431 and 0.89 mu M for SKOV-3, as for 11,4.24 mu M for A431 and 0.71 mu M for SKOV-3, respectively. Docking study was also performed to determine the possible binding model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.056

文献信息

• Synthesis and biological evaluation of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidines as dual EGFR/ErbB-2 kinase inhibitors
  作者：Siyuan Li、Chunying Guo、Hongli Zhao、Yun Tang、Minbo Lan

  DOI：10.1016/j.bmc.2011.11.056

  日期：2012.1

  A series of 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-substituted-phenoxy)pyrimidine derivatives were elaborately designed based on the skeleton of Lapatinib, and evaluated for their potential to inhibit epidermal growth factor receptor (EGFR) and ErbB-2 tyrosine kinase activities and antiproliferative activities against A431 and SKOV-3 cell lines. Among these synthesized pyrimidine derivatives, 4-[3-chloro-4-(3-fluorob enzyloxy)anilino]-6-(3-acrylamidophenoxy)pyrimidine (6), 4-13-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3cyanoacetamidophenoxy)pyrimidine (9), 4-[3-chloro-4-(3-fluorobenzyloxy)anilino)-6-(3-[6-(4-amino)pyri midinyl]amino) phenoxy)pyrimidine (11) and 4-[3-chloro-4-(3-fluorobenzyloxy)anilino]-6-(3-phenoxyacetamidophenoxy)pyrimidine (14) could significantly inhibit dual EGFR/ErbB-2 kinase activities (IC50 = 37/29 nM, 48/38 nM, 61/42 nM, 65/79 nM, respectively). And compounds 6 and 11 also showed the most potent antiproliferative activities in vitro, with the IC50 value of 6 being 3.25 mu M for A431 and 0.89 mu M for SKOV-3, as for 11,4.24 mu M for A431 and 0.71 mu M for SKOV-3, respectively. Docking study was also performed to determine the possible binding model. (C) 2011 Elsevier Ltd. All rights reserved.