N-(4-fluorobenzyl)-2-(benzyloxy)-7-cyano-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide | 1609575-95-2

• 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-(benzyloxy)-7-cyano-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
• CAS: 1609575-95-2
• 化学式: C₂₅H₁₈FN₃O₄
• 分子量: 443.434
• InChiKey: XLGIMWJPBKQATE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.21
• 重原子数：
  33.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  99.5
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-2-(benzyloxy)-7-cyano-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.0h， 以35%的产率得到N-(4-fluorobenzyl)-7-cyano-2,3-dihydroxy-1-oxo-1,2-dihydroisoquinoline-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
• 作为产物：
  描述：

  尼达尼布杂质82 在 硝酸 、 potassium hydroxide 、 sodium nitrite 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 0.33h， 生成 N-(4-fluorobenzyl)-2-(benzyloxy)-7-cyano-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