7-[4-(2-Methoxyphenyl)piperazin-1-yl]-1-methyl-4-oxo-quinoline-3-carboxylic acid

• 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: 7-[4-(2-Methoxyphenyl)piperazin-1-yl]-1-methyl-4-oxo-quinoline-3-carboxylic acid
• 英文别名: 7-[4-(2-methoxyphenyl)piperazin-1-yl]-1-methyl-4-oxoquinoline-3-carboxylic acid
• 化学式: C₂₂H₂₃N₃O₄
• 分子量: 393.442
• InChiKey: CLBGWXFDJITOAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl 2-(2,4-dichlorobenzoyl)-3-ethoxyacrylate 在 tetrafluoroboric acid 、 potassium carbonate 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 7-[4-(2-Methoxyphenyl)piperazin-1-yl]-1-methyl-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Structure Modifications of 6-Aminoquinolones with Potent Anti-HIV Activity

  摘要：

  We have recently discovered that 6-aminoquinolone derivatives could be valid leads for the development of new anti-HIV agents because of their new and diversified mode of action. In fact, studies carried out on the lead WM5 showed that this derivative is able to inhibit the Tat-mediated long terminal repeat driven transcription, an essential step in the HIV-1 replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of an enlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino derivatives to be obtained and the structure-activity relationship to be delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replication at 50% inhibitory concentration in the range of 0.0087-0.7 mug/mL in MT-4, PBMCs and CEM cell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEM cell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the new, potent 6-aminoquinolones interact at a postintegration step in the replication cycle of HIV.

  DOI：

  10.1021/jm049721p

文献信息

• Structure Modifications of 6-Aminoquinolones with Potent Anti-HIV Activity
  作者：Oriana Tabarrini、Miguel Stevens、Violetta Cecchetti、Stefano Sabatini、Micaela Dell'Uomo、Giuseppe Manfroni、Manlio Palumbo、Christophe Pannecouque、Erik De Clercq、Arnaldo Fravolini

  DOI：10.1021/jm049721p

  日期：2004.10.1

  We have recently discovered that 6-aminoquinolone derivatives could be valid leads for the development of new anti-HIV agents because of their new and diversified mode of action. In fact, studies carried out on the lead WM5 showed that this derivative is able to inhibit the Tat-mediated long terminal repeat driven transcription, an essential step in the HIV-1 replication cycle. Thus, starting from lead WM5, we performed the design and synthesis of an enlarged series of 6-aminoquinolones, which permitted some very potent anti-HIV 6-amino derivatives to be obtained and the structure-activity relationship to be delineated. Some derivatives, 26c, 26e, 26i, and 26j, proved to be highly effective in inhibiting HIV replication at 50% inhibitory concentration in the range of 0.0087-0.7 mug/mL in MT-4, PBMCs and CEM cell lines coupled with positive selectivity indexes that reach values higher than 1000 on CEM cell lines for compounds 26e and 26i. Time-of-addition experiments clearly confirm that the new, potent 6-aminoquinolones interact at a postintegration step in the replication cycle of HIV.