N-(4-methoxybenzyl)-2,3-dihydroxy-7-nitro-1-oxo-1,2-dihydroisoquinoline-4-carboxamide | 1383785-63-4

• 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-methoxybenzyl)-2,3-dihydroxy-7-nitro-1-oxo-1,2-dihydroisoquinoline-4-carboxamide
• 英文别名: 2,3-dihydroxy-N-[(4-methoxyphenyl)methyl]-7-nitro-1-oxo-isoquinoline-4-carboxamide；2,3-dihydroxy-N-[(4-methoxyphenyl)methyl]-7-nitro-1-oxoisoquinoline-4-carboxamide
• CAS: 1383785-63-4
• 化学式: C₁₈H₁₅N₃O₇
• 分子量: 385.333
• InChiKey: WJQHJGWVZWXZIU-UHFFFAOYSA-N

物化性质

• 密度：
  1.581±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氟-5-硝基苯甲酸 在 氯化亚砜 、 三氯化硼 、 sodium hydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 反应 55.5h， 生成 N-(4-methoxybenzyl)-2,3-dihydroxy-7-nitro-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

文献信息

• 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.