6-benzyl-4-benzyloxyquinoline-3-carboxylic acid | 1177256-06-2

• 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
• 英文名称: 6-benzyl-4-benzyloxyquinoline-3-carboxylic acid
• 英文别名: 6-Benzyl-4-phenylmethoxyquinoline-3-carboxylic acid
• CAS: 1177256-06-2
• 化学式: C₂₄H₁₉NO₃
• 分子量: 369.42
• InChiKey: RZDHUNILRSXAMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-benzyl-4-benzyloxyquinoline-3-carboxylic acid 在 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以65%的产率得到6-benzyl-4-benzyloxyquinoline-3-carboxamide
  参考文献：
  名称：

  Quinolone Carboxylic Acids as a Novel Monoketo Acid Class of Human Immunodeficiency Virus Type 1 Integrase Inhibitors

  摘要：

  Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto-enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited marked antiretroviral activity. Here, we show the synthesis and the detailed structure-activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)- 1-((2,S)-1-hydroxy-3,3-dimethylbutan-2-yl)-7-methoxy-4-oxo- 1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nM in the strand transfer assay and an ED50 of 0.6 nM in the antiviral assay, and 6-(3-chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-4-dihydroquinoline-3-carboxylic acid 49, which had an IC50 of 7.2 nM and an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrase-catalyzed strand transfer processes than 3'-processing reactions, as is the case with the keto-enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.

  DOI：

  10.1021/jm900460z
• 作为产物：
  描述：

  6-benzyl-4-benzyloxyquinoline-3-carboxylic acid ethyl ester 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以70%的产率得到6-benzyl-4-benzyloxyquinoline-3-carboxylic acid
  参考文献：
  名称：

  Quinolone Carboxylic Acids as a Novel Monoketo Acid Class of Human Immunodeficiency Virus Type 1 Integrase Inhibitors

  摘要：

  Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto-enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited marked antiretroviral activity. Here, we show the synthesis and the detailed structure-activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)- 1-((2,S)-1-hydroxy-3,3-dimethylbutan-2-yl)-7-methoxy-4-oxo- 1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nM in the strand transfer assay and an ED50 of 0.6 nM in the antiviral assay, and 6-(3-chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-4-dihydroquinoline-3-carboxylic acid 49, which had an IC50 of 7.2 nM and an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrase-catalyzed strand transfer processes than 3'-processing reactions, as is the case with the keto-enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.

  DOI：

  10.1021/jm900460z