4-氧代-2-苯基-1H-喹啉-7-羧酸甲酯 | 825620-22-2

• 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
• 中文名称: 4-氧代-2-苯基-1H-喹啉-7-羧酸甲酯
• 英文名称: 4-hydroxy-2-phenylquinoline-1-carboxylic acid methyl ester
• 英文别名: methyl 4-oxo-2-phenyl-1H-quinoline-7-carboxylate
• CAS: 825620-22-2
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: GSAWVSUQLRKNAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基苯甲酸甲酯 在 3-氨基苯甲酸甲酯盐酸盐 作用下， 以 二苯醚 、 甲苯 为溶剂， 反应 1.0h， 生成 4-氧代-2-苯基-1H-喹啉-7-羧酸甲酯
  参考文献：
  名称：

  A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease:  Discovery of Potent and Specific Tripeptide Inhibitors

  摘要：

  The inadequate efficacy and tolerability of current therapies for the infectious liver disease caused by the hepatitis C virus have warranted significant efforts in the development of new therapeutics. We have previously reported competitive peptide inhibitors of the NS3 serine protease based on the N-terminal cleavage products of peptide substrates. A detailed study of the interactions of these substrate-based inhibitors with the different subsites of the serine protease active site led to the discovery of novel residues that increased the affinity of the inhibitors. In this paper, we report the combination of the best binding residues in a tetrapeptide series that resulted in extremely potent inhibitors that bind exquisitely well to this enzyme. A substantial increase in potency was obtained with the simultaneous introduction of a 7-methoxy-2-phenyl-4-quinolinoxy moiety at the gamma-position of the P2 proline and a tert-leucine as a P3 residue. The increase in potency allowed for the further truncation and led to the identification of tripeptide inhibitors. Structure activity relationship studies on this inhibitor series led to the identification of carbamate-containing tripeptides that are able to inhibit replication of subgenomic HCV RNA in cell culture with potencies below 1 muM. This inhibitor series has the potential of becoming antiviral agents for the treatment of HCV infections.

  DOI：

  10.1021/jm0494523

文献信息

• Synthesis of 4-Quinolones via a Carbonylative Sonogashira Cross-Coupling Using Molybdenum Hexacarbonyl as a CO Source
  作者：Linda Åkerbladh、Patrik Nordeman、Matyas Wejdemar、Luke R. Odell、Mats Larhed

  DOI：10.1021/jo502400h

  日期：2015.2.6

  A palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence for the preparation of functionalized 4-quinolones from 2-iodoanilines and alkynes via two different protocols is described. The first method (A) yields the cyclized products after only 20 min of microwave (MW) heating at 120 degrees C. The second method (B) is a gas-free one-pot two-step sequence which runs at room temperature, allowing the use of sensitive substituents (e.g., nitro and bromide groups). For both protocols, molybdenum hexacarbonyl was used as a solid source of CO.
• A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease:  Discovery of Potent and Specific Tripeptide Inhibitors
  作者：Montse Llinàs-Brunet、Murray D. Bailey、Elise Ghiro、Vida Gorys、Ted Halmos、Martin Poirier、Jean Rancourt、Nathalie Goudreau

  DOI：10.1021/jm0494523

  日期：2004.12.1

  The inadequate efficacy and tolerability of current therapies for the infectious liver disease caused by the hepatitis C virus have warranted significant efforts in the development of new therapeutics. We have previously reported competitive peptide inhibitors of the NS3 serine protease based on the N-terminal cleavage products of peptide substrates. A detailed study of the interactions of these substrate-based inhibitors with the different subsites of the serine protease active site led to the discovery of novel residues that increased the affinity of the inhibitors. In this paper, we report the combination of the best binding residues in a tetrapeptide series that resulted in extremely potent inhibitors that bind exquisitely well to this enzyme. A substantial increase in potency was obtained with the simultaneous introduction of a 7-methoxy-2-phenyl-4-quinolinoxy moiety at the gamma-position of the P2 proline and a tert-leucine as a P3 residue. The increase in potency allowed for the further truncation and led to the identification of tripeptide inhibitors. Structure activity relationship studies on this inhibitor series led to the identification of carbamate-containing tripeptides that are able to inhibit replication of subgenomic HCV RNA in cell culture with potencies below 1 muM. This inhibitor series has the potential of becoming antiviral agents for the treatment of HCV infections.