N-(4-fluorobenzyl)-2-hydroxy-7-methoxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide | 1383785-73-6

• 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: N-(4-fluorobenzyl)-2-hydroxy-7-methoxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
• 英文别名: N-(4-fluorobenzyl)-2-hydroxy-7-methoxy-1,3-dioxo-1,2,3,4-tetrahydroisoguinoline-4-carboxamide；N-[(4-fluorophenyl)methyl]-2-hydroxy-7-methoxy-1,3-dioxo-4H-isoquinoline-4-carboxamide
• CAS: 1383785-73-6
• 化学式: C₁₈H₁₅FN₂O₅
• 分子量: 358.326
• InChiKey: WMBKQYWRPPGSCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 5%-palladium/activated carbon 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 二异丙胺 、 potassium hydroxide 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 43.0h， 生成 N-(4-fluorobenzyl)-2-hydroxy-7-methoxy-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
  参考文献：
  名称：

  Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors

  摘要：

  We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range associated with low micromolar anti-HIV activities were obtained. We investigated the influence of substitution at position 7 on biological activity. Introduction of electron-withdrawing functional groups such as the nitro moiety at position 7 led to a noticeable improvement of antiviral activity, down to low nanomolar anti-HIV potencies, with advantageous therapeutic indexes going close to those of the clinically used raltegravir and retained potencies against a panel of IN mutants.

  DOI：

  10.1021/jm500109z

文献信息

• [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。
• 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.
• Investigation of a Novel Series of 2-Hydroxyisoquinoline-1,3(2<i>H</i>,4<i>H</i>)-diones as Human Immunodeficiency Virus Type 1 Integrase Inhibitors
  作者：Virginie Suchaud、Fabrice Bailly、Cedric Lion、Christina Calmels、Marie-Line Andréola、Frauke Christ、Zeger Debyser、Philippe Cotelle

  DOI：10.1021/jm500109z

  日期：2014.6.12

  We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong human immunodeficiency virus type 1 integrase (HIV-1 IN) inhibitors in the low nanomolar range associated with low micromolar anti-HIV activities were obtained. We investigated the influence of substitution at position 7 on biological activity. Introduction of electron-withdrawing functional groups such as the nitro moiety at position 7 led to a noticeable improvement of antiviral activity, down to low nanomolar anti-HIV potencies, with advantageous therapeutic indexes going close to those of the clinically used raltegravir and retained potencies against a panel of IN mutants.