1-[3-Chloro-4-(6-methoxy-4-oxochromen-2-yl)phenyl]-3-(3-chlorophenyl)urea | 1388722-96-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 1-[3-Chloro-4-(6-methoxy-4-oxochromen-2-yl)phenyl]-3-(3-chlorophenyl)urea
• 英文别名: 1-[3-chloro-4-(6-methoxy-4-oxochromen-2-yl)phenyl]-3-(3-chlorophenyl)urea
• CAS: 1388722-96-0
• 化学式: C₂₃H₁₆Cl₂N₂O₄
• 分子量: 455.297
• InChiKey: WDHJEKGGDAHKNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-methoxy-2'-chloro-4'-aminoflavone 、 间氯苯异氰酸酯 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 以67%的产率得到1-[3-Chloro-4-(6-methoxy-4-oxochromen-2-yl)phenyl]-3-(3-chlorophenyl)urea
  参考文献：
  名称：

  Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl)phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment

  摘要：

  Based on the roles of Raf1 and JNK1 in hepatocarcinoma development, scaffold-based drug design was employed to produce a series of compounds, which subsequently were synthesized and explored as potential dual inhibitors Raf1 and JNK1 kinases for anti-tumor treatment. The compound 1-(3-chloro-4-(6-ethyl-4-oxo-4H-chromen-2-yl)phenyl)-3-(4-chloro-phenyl)urea (3d) showed 66%, 67% and 13% inhibition rate at 50 mu M against Raf1, JNK1 and p38-alpha, respectively, but no effect on ERK1 and ERK2, and inhibited the expression of pERK1/2 markedly and HepG2 cells proliferation with IC50 at 8.3 mu M. Furthermore, 3d showed lower toxicity against normal liver cell-lines QSG7701 and HL7702. Molecular docking study further showed that 3d can fit into binding domain of JNK1 and Raf1. Our data suggested the activities of 3d were associated with dual inhibition of JNK1 and Raf1 kinases. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.006

文献信息

• Exploration of 1-(3-chloro-4-(4-oxo-4H-chromen-2-yl)phenyl)-3-phenylurea derivatives as selective dual inhibitors of Raf1 and JNK1 kinases for anti-tumor treatment
  作者：Feng Jin、Dan Gao、Cunlong Zhang、Feng Liu、Bizhu Chu、Yan Chen、Yu Zong Chen、Chunyan Tan、Yuyang Jiang

  DOI：10.1016/j.bmc.2012.04.006

  日期：2013.2

  Based on the roles of Raf1 and JNK1 in hepatocarcinoma development, scaffold-based drug design was employed to produce a series of compounds, which subsequently were synthesized and explored as potential dual inhibitors Raf1 and JNK1 kinases for anti-tumor treatment. The compound 1-(3-chloro-4-(6-ethyl-4-oxo-4H-chromen-2-yl)phenyl)-3-(4-chloro-phenyl)urea (3d) showed 66%, 67% and 13% inhibition rate at 50 mu M against Raf1, JNK1 and p38-alpha, respectively, but no effect on ERK1 and ERK2, and inhibited the expression of pERK1/2 markedly and HepG2 cells proliferation with IC50 at 8.3 mu M. Furthermore, 3d showed lower toxicity against normal liver cell-lines QSG7701 and HL7702. Molecular docking study further showed that 3d can fit into binding domain of JNK1 and Raf1. Our data suggested the activities of 3d were associated with dual inhibition of JNK1 and Raf1 kinases. (C) 2012 Elsevier Ltd. All rights reserved.