4-methylbenzyl 6-amino-7-chloro-1-[2-fluoro-4-(trifluoromethyl)benzyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate | 1481640-44-1

• 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-methylbenzyl 6-amino-7-chloro-1-[2-fluoro-4-(trifluoromethyl)benzyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylate
• 英文别名: (4-Methylphenyl)methyl 6-amino-7-chloro-1-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-4-oxoquinoline-3-carboxylate；(4-methylphenyl)methyl 6-amino-7-chloro-1-[[2-fluoro-4-(trifluoromethyl)phenyl]methyl]-4-oxoquinoline-3-carboxylate
• CAS: 1481640-44-1
• 化学式: C₂₆H₁₉ClF₄N₂O₃
• 分子量: 518.895
• InChiKey: OJTGPAKFRKHUFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid 在 盐酸 、 水 、 铁粉 、 potassium carbonate 、 sodium chloride 作用下， 以 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0~150.0 ℃ 、1.5 MPa 条件下， 反应 53.25h， 生成 4-methylbenzyl 6-amino-7-chloro-1-[2-fluoro-4-(trifluoromethyl)benzyl]-4-oxo-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

文献信息

• The Versatile Nature of the 6-Aminoquinolone Scaffold: Identification of Submicromolar Hepatitis C Virus NS5B Inhibitors
  作者：Giuseppe Manfroni、Rolando Cannalire、Maria Letizia Barreca、Neerja Kaushik-Basu、Pieter Leyssen、Johan Winquist、Nunzio Iraci、Dinesh Manvar、Jan Paeshuyse、Rupa Guhamazumder、Amartya Basu、Stefano Sabatini、Oriana Tabarrini、U. Helena Danielson、Johan Neyts、Violetta Cecchetti

  DOI：10.1021/jm401362f

  日期：2014.3.13

  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.