N-(1,3-dihydro-6,7-dimethoxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyl)-4-fluorobenzenesulfonamide | 1003850-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-(1,3-dihydro-6,7-dimethoxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyl)-4-fluorobenzenesulfonamide
• 英文别名: N-(1,3-dihydro-6,7-dimethoxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyI)-4-flourobenzesulfonamide；N-(4,5-dimethoxy-3-oxo-1H-isoindol-2-yl)-4-fluoro-N-(4-fluorophenyl)sulfonylbenzenesulfonamide
• CAS: 1003850-93-8
• 化学式: C₂₂H₁₈F₂N₂O₇S₂
• 分子量: 524.523
• InChiKey: FTPYUMMOLBDCGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-(1,3-dihydro-6,7-dimethoxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyl)-4-fluorobenzenesulfonamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 N-(1,3-dihydro-6,7-dihydroxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyI)-4-flourobenzesulfonamide 、 N-(1,3-dihydro-6,7-dihydroxy-1-oxo-2H-isoindol-2-yl)-4-flourobenzesulfonamide
  参考文献：
  名称：

  2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-Based HIV-1 Integrase Inhibitors

  摘要：

  The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.

  DOI：

  10.1021/jm070715d
• 作为产物：
  描述：

  2-amino-2,3-dihydro-6,7-dimethoxy-1H-isoindol-1-one 、 4-氟苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以52%的产率得到N-(1,3-dihydro-6,7-dimethoxy-1-oxo-2H-isoindol-2-yl)-N-(4-fluorobenzenesulfonyl)-4-fluorobenzenesulfonamide
  参考文献：
  名称：

  2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-Based HIV-1 Integrase Inhibitors

  摘要：

  The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.

  DOI：

  10.1021/jm070715d

文献信息

• [EN] HYDRAZIDE, AMIDE, PHTHALIMIDE AND PHTHALHYDRAZIDE ANALOGS AS INHIBITORS OF RETROVIRAL INTEGRASE<br/>[FR] ANALOGUES D'HYDRAZIDE, D'AMIDE, DE PHTALIMIDE ET DE PHTALHYDRAZIDE EN TANT QU'INHIBITEURS DE L'INTÉGRASE RÉTROVIRALE
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2009026248A2

  公开（公告）日：2009-02-26

  The present invention provides catechol-containing hydrazides, amides, phthalimide and phthalhydrazide analogs. These compounds are inhibitors of retroviral integrase, an essential enzyme for the proliferation of retroviruses such as HIV-1. Also provided are pharmaceutical compositions comprising at least one of the catechol-containing hydrazides, amides, phthalimide or phthalhydrazide analogs and a method of using the hydrazide, amide, phthalimide and phthalhydrazide analogs to inhibit retroviral proliferation and as therapeutics for the treatment of AIDS.
• 2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-Based HIV-1 Integrase Inhibitors
  作者：Xue Zhi Zhao、Elena A. Semenova、B. Christie Vu、Kasthuraiah Maddali、Christophe Marchand、Stephen H. Hughes、Yves Pommier、Terrence R. Burke

  DOI：10.1021/jm070715d

  日期：2008.1.1

  The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.