Ethyl 6-fluoro-1-(2-hydroxyethoxymethyl)-4-oxo-quinoline-3-carboxylate | 877831-08-8

• 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 6-fluoro-1-(2-hydroxyethoxymethyl)-4-oxo-quinoline-3-carboxylate
• 英文别名: ethyl 6-fluoro-1-(2-hydroxyethoxymethyl)-4-oxoquinoline-3-carboxylate
• CAS: 877831-08-8
• 化学式: C₁₅H₁₆FNO₅
• 分子量: 309.294
• InChiKey: NJRFYPAWWHNBHY-UHFFFAOYSA-N

物化性质

• 沸点：
  466.9±45.0 °C(Predicted)
• 密度：
  1.336±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 6-fluoro-1-(2-hydroxyethoxymethyl)-4-oxo-quinoline-3-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以42%的产率得到6-fluoro-1,4-dihydro-1-<(2-hydroxyethoxy)methyl>-4-oxo-3-quinolinecarboxylic acid
  参考文献：
  名称：

  Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues

  摘要：

  Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-1) and 1-[(2-hydroxy-ethoxy)methyl]-4(1H) quinolone-3-carboxylic acids (3a-j and 31) were synthesized and 2a-j, 21 and 3a-j, 31 were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: sitylation of the desired quinolone (BSTFA 1% TMCS) followed by equiniolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-1 were obtained in 40-77% yields. The esters 2a-j and 21 were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 mu M, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7 +/- 0.04 and 0.8 +/- 0.09 mu M, respectively. Both compounds were not toxic towards the Vero cell line. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.111
• 作为产物：
  描述：

  1,3-二氧戊环 、 6-氟-4-氧代-1,4-二氢-3-喹啉羧酸乙酯 在 三甲基氯硅烷 、 N,O-双(三甲基硅烷基)三氟乙酰胺 、 potassium iodide 、 水 、 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 Ethyl 6-fluoro-1-(2-hydroxyethoxymethyl)-4-oxo-quinoline-3-carboxylate
  参考文献：
  名称：

  氧喹啉衍生物的合成，抗病毒活性和分子模拟

  摘要：

  在本文中，我们描述了11种氧喹啉衍生物的合成，抗HIV1谱和分子模型评价。结构-活性关系分析揭示了一些立体电子性质，例如LUMO能量，偶极矩，可旋转键的数目以及与化合物效能相关的氢键供体和受体。我们还描述了取代基R 2和R 3对其生物学活性的重要性。化合物2j 因其（i）对HIV-1的高活性，（ii）PBMC的细胞毒性低，（iii）基于计算机评估而具有的低毒性风险，（iv）良好的口服理论，被确定为未来研究的主要化合物。根据Lipinski的“五分法则”，具有较高的生物利用度，（v）与目前的抗病毒药物AZT和efavirenz相比，其药物相似性和药物得分更高。

  DOI：

  10.1016/j.bmc.2009.06.037

文献信息

• Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues
  作者：Bianca d’A. Lucero、Claudia Regina B. Gomes、Izabel Christina de P.P. Frugulhetti、Letícia V. Faro、Lise Alvarenga、Maria Cecília B.V. de Souza、Thiago M.L. de Souza、Vitor F. Ferreira

  DOI：10.1016/j.bmcl.2005.10.111

  日期：2006.2

  Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-1) and 1-[(2-hydroxy-ethoxy)methyl]-4(1H) quinolone-3-carboxylic acids (3a-j and 31) were synthesized and 2a-j, 21 and 3a-j, 31 were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: sitylation of the desired quinolone (BSTFA 1% TMCS) followed by equiniolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-1 were obtained in 40-77% yields. The esters 2a-j and 21 were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 mu M, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7 +/- 0.04 and 0.8 +/- 0.09 mu M, respectively. Both compounds were not toxic towards the Vero cell line. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis, antiviral activity and molecular modeling of oxoquinoline derivatives
  作者：Fernanda da C. Santos、Paula Abreu、Helena C. Castro、Izabel C.P.P. Paixão、Claudio C. Cirne-Santos、Viveca Giongo、Juliana E. Barbosa、Bruno R. Simonetti、Valéria Garrido、Dumith Chequer Bou-Habib、David de O. Silva、Pedro N. Batalha、Jairo R. Temerozo、Thiago M. Souza、Christiane M. Nogueira、Anna C. Cunha、Carlos R. Rodrigues、Vitor F. Ferreira、Maria C.B.V. de Souza

  DOI：10.1016/j.bmc.2009.06.037

  日期：2009.8

  importance of substituents R2 and R3 for their biological activity. Compound 2j was identified as a lead compound for future investigation due to its : (i) high activity against HIV-1, (ii) low cytotoxicity in PBMC, (iii) low toxic risks based on in silico evaluation, (iv) a good theoretical oral bioavailability according to Lipinski ‘rule of five’, (v) higher druglikeness and drug-score values than current

  在本文中，我们描述了11种氧喹啉衍生物的合成，抗HIV1谱和分子模型评价。结构-活性关系分析揭示了一些立体电子性质，例如LUMO能量，偶极矩，可旋转键的数目以及与化合物效能相关的氢键供体和受体。我们还描述了取代基R 2和R 3对其生物学活性的重要性。化合物2j 因其（i）对HIV-1的高活性，（ii）PBMC的细胞毒性低，（iii）基于计算机评估而具有的低毒性风险，（iv）良好的口服理论，被确定为未来研究的主要化合物。根据Lipinski的“五分法则”，具有较高的生物利用度，（v）与目前的抗病毒药物AZT和efavirenz相比，其药物相似性和药物得分更高。