1-(2-tert-butoxycarbonylethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester | 1177256-48-2

• 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: 1-(2-tert-butoxycarbonylethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 6-[(2,3-dichlorophenyl)methyl]-1-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-4-oxoquinoline-3-carboxylate
• CAS: 1177256-48-2
• 化学式: C₂₆H₂₇Cl₂NO₅
• 分子量: 504.41
• InChiKey: RYSRMCORYYSFRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-tert-butoxycarbonylethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 在 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 1.5h， 以96%的产率得到1-(2-carboxyethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
  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-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 、 丙烯酸叔丁酯 在 苄基三甲基氢氧化铵 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以50%的产率得到1-(2-tert-butoxycarbonylethyl)-6-(2,3-dichlorobenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
  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