ethyl 1-[(diisopropoxyphosphoryl)methyl]-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate | 1389323-25-4

• 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 1-[(diisopropoxyphosphoryl)methyl]-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 1-[di(propan-2-yloxy)phosphorylmethyl]-7-fluoro-4-oxoquinoline-3-carboxylate
• CAS: 1389323-25-4
• 化学式: C₁₉H₂₅FNO₆P
• 分子量: 413.383
• InChiKey: LVCZHGQNDMEBFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  diethyl 2-(((3-fluorophenyl)amino)methylene)malonate 在 Dowtherm A 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 ethyl 1-[(diisopropoxyphosphoryl)methyl]-7-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1

  摘要：

  The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1-[(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC50 values of 0.4 +/- 0.2 mu M (3f) and 0.2 +/- 0.005 mu M (3g) and selectivity index values (SI) of 6240 and 14675, respectively. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.06.020

文献信息

• Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1
  作者：Letícia V. Faro、Jéssica M. de Almeida、Cláudio C. Cirne-Santos、Viveca A. Giongo、Luís R. Castello-Branco、Ingrid de B. Oliveira、Juliana E.F. Barbosa、Anna C. Cunha、Vítor F. Ferreira、Marcos C. de Souza、Izabel C.N.P. Paixão、Maria Cecília B.V. de Souza

  DOI：10.1016/j.bmcl.2012.06.020

  日期：2012.8

  The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1-[(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC50 values of 0.4 +/- 0.2 mu M (3f) and 0.2 +/- 0.005 mu M (3g) and selectivity index values (SI) of 6240 and 14675, respectively. (C) 2012 Published by Elsevier Ltd.