methyl 2-(benzyloxy)-7-phenylacetamido-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate | 1383786-41-1

• 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)-7-phenylacetamido-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
• 英文别名: methyl 1,3-dioxo-7-[(2-phenylacetyl)amino]-2-phenylmethoxy-4H-isoquinoline-4-carboxylate
• CAS: 1383786-41-1
• 化学式: C₂₆H₂₂N₂O₆
• 分子量: 458.47
• InChiKey: DVGIPFVZOKZQOU-UHFFFAOYSA-N

物化性质

• 熔点：
  187-196 °C
• 密度：
  1.37±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(benzyloxy)-7-phenylacetamido-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate 、 对氟苄胺 在 5%-palladium/activated carbon 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 生成 N-(4-fluorobenzyl)-2-hydroxy-1,3-dioxo-7-phenylacetamido-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
• 作为产物：
  描述：

  methyl 2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-5-nitrobenzoate 在 5%-palladium/activated carbon 、 氢气 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 16.0h， 生成 methyl 2-(benzyloxy)-7-phenylacetamido-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate
  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