2-(4-Amino-2-chlorophenyl)-6-ethylchromen-4-one | 1388722-87-9

• 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: 2-(4-Amino-2-chlorophenyl)-6-ethylchromen-4-one
• CAS: 1388722-87-9
• 化学式: C₁₇H₁₄ClNO₂
• 分子量: 299.757
• InChiKey: IWJNXRNHGXBQCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对氟苯甲酸 、 2-(4-Amino-2-chlorophenyl)-6-ethylchromen-4-one 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以65%的产率得到N-(3-chloro-4-(6-ethyl-4-oxo-4H-chromen-2-yl)phenyl)-2-(3-fluorophenyl)acetamide
  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
• 作为产物：
  描述：

  6-ethyl-2'-chloro-4'-nitroflavone 在 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以88%的产率得到2-(4-Amino-2-chlorophenyl)-6-ethylchromen-4-one
  参考文献：
  名称：

  选择性靶向肝癌细胞的 2'-Chloro-4'-氨基黄酮衍生物：便捷的合成过程、G2/M 细胞周期阻滞和凋亡触发

  摘要：

  通过简便的合成工艺合成了一系列2'-氯-4'-硝基黄酮和2'-氯-4'-氨基黄酮衍生物。评估了这些化合物对肝癌细胞 (HepG2)、乳腺腺癌细胞 (MCF-7) 和人类慢性粒细胞白血病细胞 (K562) 的体外抗增殖能力。大多数合成化合物对HepG2细胞具有显着的抗增殖活性，而对MCF-7细胞和K562细胞的活性很小。特别是，化合物 4c 和 4e 对 HepG2 细胞表现出高抗增殖活性，IC50 约为 2.0 µM。对正常人肝细胞的进一步毒性筛选表明，一些化合物对正常肝细胞的毒性较低，其中4e对QSG7701和HL7702细胞的作用非常弱，IC50值>100和50 μM，分别。选择在氨基取代的黄酮中具有最佳抗增殖活性 (IC50 = 2.0 µM) 的化合物 4c 以进一步评估其对细胞凋亡和细胞周期的影响。HepG2 细胞暴露于这种浓度为 10 µM 的化合物中，这会导致细胞核分解和 DNA

  DOI：

  10.1002/ardp.201100383

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.
• 2′-Chloro-4′-aminoflavone Derivatives Selectively Targeting Hepatocarcinoma Cells: Convenient Synthetic Process, G2/M Cell Cycle Arrest and Apoptosis Triggers
  作者：Feng Jin、Nannan Zhang、Chunyan Tan、Dan Gao、Cunlong Zhang、Feng Liu、Zhe Chen、Chunmei Gao、Hongxia Liu、Shangfu Li、Yuyang Jiang

  DOI：10.1002/ardp.201100383

  日期：2012.7

  A series of 2′‐chloro‐4′‐nitroflavone and 2′‐chloro‐4′‐aminoflavone derivatives were synthesized by a convenient synthetic process. The in vitro anti‐proliferation ability of these compounds was evaluated against hepatocarcinoma cells (HepG2), breast adenocarcinoma cells (MCF‐7), and human chronic myelogenous leukemia cells (K562). Most of synthetic compounds possessed notable anti‐proliferation activity

  通过简便的合成工艺合成了一系列2'-氯-4'-硝基黄酮和2'-氯-4'-氨基黄酮衍生物。评估了这些化合物对肝癌细胞 (HepG2)、乳腺腺癌细胞 (MCF-7) 和人类慢性粒细胞白血病细胞 (K562) 的体外抗增殖能力。大多数合成化合物对HepG2细胞具有显着的抗增殖活性，而对MCF-7细胞和K562细胞的活性很小。特别是，化合物 4c 和 4e 对 HepG2 细胞表现出高抗增殖活性，IC50 约为 2.0 µM。对正常人肝细胞的进一步毒性筛选表明，一些化合物对正常肝细胞的毒性较低，其中4e对QSG7701和HL7702细胞的作用非常弱，IC50值>100和50 μM，分别。选择在氨基取代的黄酮中具有最佳抗增殖活性 (IC50 = 2.0 µM) 的化合物 4c 以进一步评估其对细胞凋亡和细胞周期的影响。HepG2 细胞暴露于这种浓度为 10 µM 的化合物中，这会导致细胞核分解和 DNA