methyl 2-hydroxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate | 1278482-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: methyl 2-hydroxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
• 英文别名: 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione；methyl 2-hydroxy-1,3-dioxo-4H-isoquinoline-4-carboxylate
• CAS: 1278482-16-8
• 化学式: C₁₁H₉NO₅
• 分子量: 235.196
• InChiKey: LOVFGBDGBZUKPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl 2-(benzyloxy)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate 在 三氯化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 1.08h， 生成 methyl 2-hydroxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
  参考文献：
  名称：

  Magnesium Chelating 2-Hydroxyisoquinoline-1,3(2H,4H)-diones, as Inhibitors of HIV-1 Integrase and/or the HIV-1 Reverse Transcriptase Ribonuclease H Domain: Discovery of a Novel Selective Inhibitor of the Ribonuclease H Function

  摘要：

  2-Hydroxyisoquinoline-1,3(2H,4H)-dione was recently discovered as a scaffold for the inhibition of HIV-1 integrase and the ribonuclease H function of HIV-1 reverse transcriptase. First, we investigate its interaction with Mg2+ and Mn2+ using different spectroscopic techniques and report that 2-hydroxyisoquinoline-1,3(2H,4H)-dione forms a 1:1 complex with Mg2+ but a 1:2 complex with Mn2+. The complex formation requires enolization of the ligand. ESR spectroscopy shows a redox reaction between the ligand and Mn2+ producing superoxide anions. Second, 2-hydroxyisoquinoline-1,3(2H,4H)-dione, its magnesium complex, and its 4-methyl and 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-diones were tested as inhibitors of HIV-1 integrase, reverse transcriptase ribonuclease H, and DNA polymerase functions. Their antiviral activities were evaluated and 2-hydroxy-4-methoxycarbonyl-isoquinoline-1,3(2H,4H)-dione was found to inhibit the viral replication of HIV-1 in MT-4 cells. Cross-resistance was measured for this compound on three different viral strains. Experimental data suggest that the antiviral activity of 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione is probably due to the RNase H inhibition.

  DOI：

  10.1021/jm1014692

文献信息

• N-HYDROXYISOQUINOLINEDIONE INHIBITORS OF HBV REPLICATION
  申请人：Saint Louis University

  公开号：US20190070165A1

  公开（公告）日：2019-03-07

  In some aspects, the present disclosure provides compounds of the formula: Formula (I) wherein the variables are defined herein are provided, which may be used to inhibit viral replication. In some embodiments, these compounds may be used to treat an infection of hepatitis B virus.
• [EN] N-HYDROXYISOQUINOLINEDIONE INHIBITORS OF HBV REPLICATION<br/>[FR] INHIBITEURS DE RÉPLICATION DU VHB DE TYPE N-HYDROXYISOQUINOLINEDIONE
  申请人：UNIV SAINT LOUIS

  公开号：WO2017161133A1

  公开（公告）日：2017-09-21

  In some aspects, the present disclosure provides compounds of the formula: Formula (I) wherein the variables are defined herein are provided, which may be used to inhibit viral replication. In some embodiments, these compounds may be used to treat an infection of hepatitis B virus.
• Magnesium Chelating 2-Hydroxyisoquinoline-1,3(2<i>H</i>,4<i>H</i>)-diones, as Inhibitors of HIV-1 Integrase and/or the HIV-1 Reverse Transcriptase Ribonuclease H Domain: Discovery of a Novel Selective Inhibitor of the Ribonuclease H Function
  作者：Muriel Billamboz、Fabrice Bailly、Cédric Lion、Nadia Touati、Hervé Vezin、Christina Calmels、Marie-Line Andréola、Frauke Christ、Zeger Debyser、Philippe Cotelle

  DOI：10.1021/jm1014692

  日期：2011.3.24

  2-Hydroxyisoquinoline-1,3(2H,4H)-dione was recently discovered as a scaffold for the inhibition of HIV-1 integrase and the ribonuclease H function of HIV-1 reverse transcriptase. First, we investigate its interaction with Mg2+ and Mn2+ using different spectroscopic techniques and report that 2-hydroxyisoquinoline-1,3(2H,4H)-dione forms a 1:1 complex with Mg2+ but a 1:2 complex with Mn2+. The complex formation requires enolization of the ligand. ESR spectroscopy shows a redox reaction between the ligand and Mn2+ producing superoxide anions. Second, 2-hydroxyisoquinoline-1,3(2H,4H)-dione, its magnesium complex, and its 4-methyl and 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-diones were tested as inhibitors of HIV-1 integrase, reverse transcriptase ribonuclease H, and DNA polymerase functions. Their antiviral activities were evaluated and 2-hydroxy-4-methoxycarbonyl-isoquinoline-1,3(2H,4H)-dione was found to inhibit the viral replication of HIV-1 in MT-4 cells. Cross-resistance was measured for this compound on three different viral strains. Experimental data suggest that the antiviral activity of 2-hydroxy-4-methoxycarbonylisoquinoline-1,3(2H,4H)-dione is probably due to the RNase H inhibition.