7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 99866-50-9

• 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: 7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• CAS: 99866-50-9
• 化学式: C₁₁H₇ClN₂O₅
• 分子量: 282.64
• InChiKey: MEUKCCROORJVFU-UHFFFAOYSA-N

物化性质

• 沸点：
  510.3±50.0 °C(Predicted)
• 密度：
  1.651±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  102.44
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7-chloro-1-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 二苯醚 作用下， 反应 15.0h， 生成 7-Chloro-1-methyl-6-nitro-4(1H)-quinolinone
  参考文献：
  名称：

  抗HIV 6-去氟喹诺酮类药物的构效关系研究。

  摘要：

  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。

  DOI：

  10.1021/jm701585h

文献信息

• Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands
  作者：Luca Sancineto、Nunzio Iraci、Maria Letizia Barreca、Serena Massari、Giuseppe Manfroni、Gianmarco Corazza、Violetta Cecchetti、Alessandro Marcello、Dirk Daelemans、Christophe Pannecouque、Oriana Tabarrini

  DOI：10.1016/j.bmc.2014.07.018

  日期：2014.9

  It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives.