ethyl 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate | 173061-57-9

• 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: ethyl 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
• CAS: 173061-57-9
• 化学式: C₁₃H₁₁ClN₂O₅
• 分子量: 310.694
• InChiKey: SHZTXGBIAQCQCY-UHFFFAOYSA-N

物化性质

• 沸点：
  485.0±45.0 °C(Predicted)
• 密度：
  1.458±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  91.44
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 镍 sodium hydroxide 、 氢气 、 potassium carbonate 作用下， 以 乙二醇甲醚 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 20.0~100.0 ℃ 、207.73 kPa 条件下， 反应 7.5h， 生成 1-Methyl-6-(methylamino)-4-oxo-7-[4-(2-pyridyl)piperazin-1-yl]quinoline-3-carboxylic acid
  参考文献：
  名称：

  6-Aminoquinolones as New Potential Anti-HIV Agents

  摘要：

  A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC50 value was 0.1 mu M, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.

  DOI：

  10.1021/jm9903390
• 作为产物：
  描述：

  ethyl ester of 3-dimethylamino-2-(5-nitro-2,4-dichlorobenzoyl)acrylic acid 、 甲胺 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 以80%的产率得到ethyl 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  6-Aminoquinolones as New Potential Anti-HIV Agents

  摘要：

  A series of 6-aminoquinolone compounds were evaluated for their in vitro activity against human immunodeficiency virus type 1 (HIV-1). Compound 12a, bearing a methyl substituent at the N-1 position and a 4-(2-pyridyl)-1-piperazine moiety at the C-7 position, was the most active in inhibiting HIV-1 replication on de novo infected C8166 human lymphoblastoid cell lines. The 12a EC50 value was 0.1 mu M, a 7-20-fold lower concentration relative to that for compounds 8a and 7a containing a cyclopropyl and tert-butyl substituent at the N-1 position, respectively. When the C-6 amino group was replaced with a fluorine atom, a decreased antiviral effect was observed. The observed effects are selective, since potency is substantially reduced when testing the compounds against the herpes simplex virus type 1 (HSV-1). Active quinolone derivatives very efficiently interact with TAR RNA, which suggests a nucleic acid-targeted mechanism of action.

  DOI：

  10.1021/jm9903390

文献信息

• Structure−Activity Relationship Study on Anti-HIV 6-Desfluoroquinolones
  作者：Oriana Tabarrini、Serena Massari、Dirk Daelemans、Miguel Stevens、Giuseppe Manfroni、Stefano Sabatini、Jan Balzarini、Violetta Cecchetti、Christophe Pannecouque、Arnaldo Fravolini

  DOI：10.1021/jm701585h

  日期：2008.9.11

  recent findings that 6-aminoquinolones inhibit the HIV Tat-mediated transactivation, we have designed a broad series of derivatives identifying novel potent agents such as the 6-desfluoroquinolones 24 (HM12) and 27 (HM13), which showed pronounced anti-HIV activity in acutely, chronically, and latently HIV-1 infected cell cultures. We demonstrate here that highly potent molecules can be obtained by optimizing

  根据我们最近的发现，即6-氨基喹诺酮类药物抑制HIV Tat介导的反式激活，我们设计了一系列衍生物，这些衍生物可识别新型强效药物，例如6-去氟喹诺酮类药物24（HM12）和27（HM13），其表现出明显的在急性，慢性和潜在感染HIV-1的细胞培养物中具有抗HIV活性。我们在这里证明，通过优化喹诺酮核的各个位置上的取代基，可以获得高效能的分子。
• 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.