5-methoxy-2-phenyl-4-quinolone | 189816-03-3

• 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: 5-methoxy-2-phenyl-4-quinolone
• 英文别名: 5-Methoxy-2-phenylquinolin-4-ol；5-methoxy-2-phenyl-1H-quinolin-4-one
• CAS: 189816-03-3；258353-97-8
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: IRTIKLRZEZAMDF-UHFFFAOYSA-N

物化性质

• 沸点：
  466.4±45.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-phenyl-4-quinolone 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 生成
  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
• 作为产物：
  描述：

  5-甲氧基黄酮 在 ammonium hydroxide 、 高氯酸 作用下， 反应 10.0h， 生成 5-methoxy-2-phenyl-4-quinolone
  参考文献：
  名称：

  通过天然存在的黄烷酮中的4-烷氧基黄酮盐直接转化为2-苯基-4-喹诺酮

  摘要：

  在温和条件下，通过黄酮盐将其中5-位羟基被甲基保护的黄烷酮转化为相应的5-甲氧基-2-苯基-4-喹诺酮。黄烷酮-O-鼠李糖苷，柚皮苷也以相同的方式转化为5-甲氧基-2-苯基-4-喹诺酮-7 - O-鼠李糖苷，总产率为25％。

  DOI：

  10.1002/jhet.5570360539

文献信息

• Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 1. Identification of the 4-Quinolinecarboxamide Framework
  作者：Giuseppe A. M. Giardina、Henry M. Sarau、Carlo Farina、Andrew D. Medhurst、Mario Grugni、Luca F. Raveglia、Dulcie B. Schmidt、Roberto Rigolio、Mark Luttmann、Vittorio Vecchietti、Douglas W. P. Hay

  DOI：10.1021/jm960818o

  日期：1997.6.1

  A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO)

  基于化学上不同的NK-1受体拮抗剂，设计了一种新型的有效且选择性的非肽神经激肽3（NK-3）受体拮抗剂，其特征在于4-喹啉羧酰胺骨架。通过原型4的化学修饰促进了新型化合物33-76的表达，其特征在于使用表达人神经激肽3受体（hNK-3-CHO）的中国仓鼠卵巢（CHO）细胞膜制剂进行结合分析，并建立了明确的结构-活性关系（SAR）。从SARs（R）-N- [α-（甲氧基羰基）苄基] -2-苯基喹啉-4-羧酰胺（65，SB 218795，hNK-3-CHO结合Ki = 13 nM）出现，是最有效的化合物之一这个新颖的班级。对其他神经激肽受体（hNK-2-CHO和hNK-1-CHO）的选择性研究表明，对hNK-3的选择性是对hNK-2受体的65倍（hNK-2-CHO结合Ki = 1221 nM）。相对于hNK-1受体具有超过7000倍的选择性（hNK-1-CHO结合Ki => 100 micro
• Antimitotic Activity of 5-Hydroxy-7-methoxy-2-phenyl-4-quinolones
  作者：Mohamed Hadjeri、Eva-Laure Peiller、Chantal Beney、Nabajyoti Deka、Martin A. Lawson、Charles Dumontet、Ahcène Boumendjel

  DOI：10.1021/jm049876x

  日期：2004.9.1

  We report the synthesis of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones and their biological activity as antitumor agents. These molecules were initially evaluated for their ability to induce cell cycle arrest in the G2/M phase. Compounds that showed significant G2/M cell cycle arrest were tested for antiproliferative activity using both the MTT assay and the NCI in vitro 60 cell line human tumor screen. The 5-hydroxy-7-methoxy-2-phenyl-4-quinolone (3a) and 2-(3-fluorophenyl)-5-hydroxy-7-methoxy-4-quinolone (3f) were the most active in the cell cycle arrest test whereas 3f was found to be the most active in the MTT assay. In terms of structural requirements, we found that the presence of a 5-hydroxyl group, a 7-methoxy group, and an unsubstituted N1 were essential for the antimitotic activity. In accordance with the literature, a fluoro group at the 3'- or 2'-position and a methoxy or a chloro group at the 3'-position were found to be highly advantageous for both the cell cycle arrest and the antiproliferative activities.
• 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.
• Direct conversion to 2-phenyl-4-quinolones<i>via</i>a 4-alkoxyflavylium salt from a naturally occurring flavanone
  作者：Shingo Sato、Hironobu Kumagai、Shigeru Matsuba、Toshihiro Kumazawa、Jun-Ichi Onodera、Masanobu Suzuki

  DOI：10.1002/jhet.5570360539

  日期：1999.9

  A flavanone, in which a hydroxyl group at the 5-position was protected with a methyl group, converted to the corresponding 5-methoxy-2-phenyl-4-quinolone via flavylium salt under mild conditions. Flavanone-O-rhamnoglucoside, naringin, was also converted to 5-methoxy-2-phenyl-4-quinolon-7-O-rhamnoglucoside in the same way in an overall 25% yield.

  在温和条件下，通过黄酮盐将其中5-位羟基被甲基保护的黄烷酮转化为相应的5-甲氧基-2-苯基-4-喹诺酮。黄烷酮-O-鼠李糖苷，柚皮苷也以相同的方式转化为5-甲氧基-2-苯基-4-喹诺酮-7 - O-鼠李糖苷，总产率为25％。