methyl 2-(benzyloxy)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate | 1174226-00-6

• 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-(benzyloxy)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
• 英文别名: methyl 1,3-dioxo-2-phenylmethoxy-4H-isoquinoline-4-carboxylate
• CAS: 1174226-00-6
• 化学式: C₁₈H₁₅NO₅
• 分子量: 325.321
• InChiKey: NPUCAARDNWYGBM-UHFFFAOYSA-N

物化性质

• 熔点：
  126 °C
• 沸点：
  459.8±55.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3-methoxy-2-[2-(methoxycarbonyl)phenyl]-3-oxopropanoic acid 在 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 methyl 2-(benzyloxy)-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
  参考文献：
  名称：

  4-Substituted 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as a Novel Class of HIV-1 Integrase Inhibitors

  摘要：

  A series of 2-hydroxy-1,3-dioxoisoquinoline-4-carboxamides featuring an N-hydroxyimide chelating functionality was evaluated for their inhibitory properties against human immunodeficiency virus type 1 integrase (HIV-1 IN). Several derivatives displayed low nanomolar IC50 values comparable to that of the clinically used raltegravir. A marked effect of one compound on both primary IN-catalyzed reactions, strand transfer (ST), and 3' processing (3'-P), emphasizes a novel IN inhibition mechanism establishing it as a potential new generation IN inhibitor. Substitution of the 2-hydroxyisoquinoline-1,3-dione scaffold at position 4 by carboxamido, chains was beneficial for antiviral activity since reproducible low micromolar anti-HIV activities were obtained for the first time within this scaffold.

  DOI：

  10.1021/ml400009t

文献信息

• 2-hydroxyisoquinoline-1,3(2 H ,4 H )-diones (HIDs) as human immunodeficiency virus type 1 integrase inhibitors: Influence of the alkylcarboxamide substitution of position 4
  作者：Muriel Billamboz、Virginie Suchaud、Fabrice Bailly、Cedric Lion、Marie-Line Andréola、Frauke Christ、Zeger Debyser、Philippe Cotelle

  DOI：10.1016/j.ejmech.2016.03.083

  日期：2016.7

  Herein, we report further insight into the biological activities displayed by the 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) scaffold. Previous studies have evidenced the marked fruitful effect of substitution of this two-metal binding pharmacophore at position 4 by phenyl and benzyl carboxamido chains. Strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar

  在这里，我们报告进一步了解由2-羟基异喹啉-1,3（2 H，4 H）-二酮（HID）支架。先前的研究已经证明，在位置4处的这种由两种金属结合的药效团被苯基和苄基羧酰胺基链取代的显著作用。获得了在低纳摩尔范围内具有微摩尔（甚至低至低纳摩尔）抗HIV活性的强力人类免疫缺陷病毒1型整合酶（HIV-1 IN）抑制剂。保持这种必不可少的4-甲酰胺基功能，我们研究了各种烷基链取代苯基和苄基的影响。这项研究表明，在INSTI中发现的经常性卤代苄基药效团可以被正烷基有效取代。与六个碳的最佳长度，我们观察到的生物学概况和高抵抗力的屏障，相当于以前报道的带有4-氟苄基的命中化合物。
• [EN] 2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONES AND RELATED COMPOUNDS USEFUL AS HIV REPLICATION INHIBITORS<br/>[FR] 2 -HYDROXYISOQUINOLINE- 1, 3 ( 2H, 4H) - DIONES ET COMPOSÉS ASSOCIÉS SERVANT D'INHIBITEURS DE LA RÉPLICATION DU VIH
  申请人：UNIV LEUVEN KATH

  公开号：WO2012085003A1

  公开（公告）日：2012-06-28

  The present invention relates to compounds and compositions acting as inhibitors of HIV integrase. The compound of the invention is of Formula (I), or a tautomer (I') thereof, or a pharmaceutically acceptable salt, or solvate of said compound or tautomer thereof, wherein R1, R2, R3, R4, R5 and R6 have defined meanings.

  本发明涉及作为HIV整合酶抑制剂的化合物和组合物。该发明的化合物为式(I)的化合物，或其互变异构体(I')，或所述化合物或其互变异构体的药用可接受盐或溶剂，其中R1、R2、R3、R4、R5和R6具有定义的含义。