4-chlorobenzyl 1-(4-chlorobenzyl)-6-nitro-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate | 1481640-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-chlorobenzyl 1-(4-chlorobenzyl)-6-nitro-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate
• CAS: 1481640-62-3
• 化学式: C₃₃H₂₇Cl₂N₅O₅
• 分子量: 644.514
• InChiKey: HUFJCTZLUAWZEA-UHFFFAOYSA-N

物化性质

• 熔点：
  199-201 °C
• 沸点：
  844.3±65.0 °C(predicted)
• 密度：
  1.437±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.34
• 重原子数：
  45.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  110.81
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  4-chlorobenzyl 1-(4-chlorobenzyl)-6-nitro-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate 在 水 、 铁粉 、 sodium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以20%的产率得到4-chlorobenzyl 6-amino-1-(4-chlorobenzyl)-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate
  参考文献：
  名称：

  The Versatile Nature of the 6-Aminoquinolone Scaffold: Identification of Submicromolar Hepatitis C Virus NS5B Inhibitors

  摘要：

  We have previously reported that the 6-aminoquinolone chemotype is a privileged scaffold to obtain antibacterial and antiviral agents. Herein we describe the design, synthesis, and enzymatic and cellular characterization of new 6-aminoquinolone derivatives as potent inhibitors of NS5B polymerase, an attractive and viable therapeutic target to develop safe anti-HCV agents. The 6-amino-7-[4-(2-pyridinyl)-1-piperazinyl]quinolone derivative 8 proved to be the best compound of this series, exhibiting an IC50 value of 0.069 mu M against NS5B polymerase and selective antiviral effect (EC50 = 3.03 mu M) coupled with the absence of any cytostatic effect (CC50 > 163 mu M; SI > 54) in Huh 9-13 cells carrying a HCV genotype 1b, as measured by MTS assay. These results indicate that the 6-aminoquinolone scaffold is worthy of further investigation in the context of NS5B-targeted HCV drug discovery programs.

  DOI：

  10.1021/jm401362f
• 作为产物：
  描述：

  ethyl 3-[(4-chlorobenzyl)amino]-2-(2,4-dichloro-5-nitrobenzoyl)acrylate 在 盐酸 、 potassium carbonate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 60.0~120.0 ℃ 、1.5 MPa 条件下， 反应 49.17h， 生成 4-chlorobenzyl 1-(4-chlorobenzyl)-6-nitro-4-oxo-7-[4-(2-pyridinyl)-1-piperazinyl]-1,4-dihydro-3-quinolinecarboxylate
  参考文献：
  名称：

  The Versatile Nature of the 6-Aminoquinolone Scaffold: Identification of Submicromolar Hepatitis C Virus NS5B Inhibitors

  摘要：

  We have previously reported that the 6-aminoquinolone chemotype is a privileged scaffold to obtain antibacterial and antiviral agents. Herein we describe the design, synthesis, and enzymatic and cellular characterization of new 6-aminoquinolone derivatives as potent inhibitors of NS5B polymerase, an attractive and viable therapeutic target to develop safe anti-HCV agents. The 6-amino-7-[4-(2-pyridinyl)-1-piperazinyl]quinolone derivative 8 proved to be the best compound of this series, exhibiting an IC50 value of 0.069 mu M against NS5B polymerase and selective antiviral effect (EC50 = 3.03 mu M) coupled with the absence of any cytostatic effect (CC50 > 163 mu M; SI > 54) in Huh 9-13 cells carrying a HCV genotype 1b, as measured by MTS assay. These results indicate that the 6-aminoquinolone scaffold is worthy of further investigation in the context of NS5B-targeted HCV drug discovery programs.

  DOI：

  10.1021/jm401362f