N-(4-fluorobenzyl)-2-(benzyloxy)-1,3-dioxo-7-phenylacetamido-1,2,3,4-tetrahydroisoquinoline-4-carboxamide | 1383786-43-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: N-(4-fluorobenzyl)-2-(benzyloxy)-1,3-dioxo-7-phenylacetamido-1,2,3,4-tetrahydroisoquinoline-4-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-1,3-dioxo-7-[(2-phenylacetyl)amino]-2-phenylmethoxy-4H-isoquinoline-4-carboxamide
• CAS: 1383786-43-3
• 化学式: C₃₂H₂₆FN₃O₅
• 分子量: 551.574
• InChiKey: HBEXERRFTYFAIX-UHFFFAOYSA-N

物化性质

• 熔点：
  225-229 °C
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-2-(benzyloxy)-1,3-dioxo-7-phenylacetamido-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， 以83%的产率得到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：

  尼达尼布杂质82 在 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 4.0h， 生成 N-(4-fluorobenzyl)-2-(benzyloxy)-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

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。