N-{4-[(2-benzoylhydrazino)carbonyl]benzyl}-3-nitrobenzenesulfonamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-{4-[(2-benzoylhydrazino)carbonyl]benzyl}-3-nitrobenzenesulfonamide
• 英文别名: N-[[4-(benzamidocarbamoyl)phenyl]methyl]-3-nitrobenzenesulfonamide
• 化学式: C₂₁H₁₈N₄O₆S
• 分子量: 454.463
• InChiKey: USRCZAUSTRJMOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-[(叔丁氧羰基氨基)甲基]苯甲酸 在 Sodium tetraborate decahydrate 、 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 N-{4-[(2-benzoylhydrazino)carbonyl]benzyl}-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  Systematic variation of the benzenesulfonamide part of the GluN2A selective NMDA receptor antagonist TCN-201

  摘要：

  GluN2A subunit containing N-methyl-D-aspartate receptors (NMDARs) are highly involved in various physiological processes in the central nervous system, but also in some diseases, such as anxiety, depression and schizophrenia. However, the role of GluN2A subunit containing NMDARs in pathological processes is not exactly elucidated. In order to obtain potent and selective inhibitors of GluN2A subunit containing NMDARs, the selective negative allosteric modulator 2 was systematically modified at the benzenesulfonamide part. The activity of the test compounds was recorded in two electrode voltage clamp experiments using Xenopus laevis oocytes expressing exclusively NMDARs with GluN1a and GluN2A subunits. It was found that halogen atoms in 3-position of the benzenesulfonamide part result in high GluN2A antagonistic activity. With an IC50 value of 204 nM the 3-bromo derivative 5i (N-{4-[(2-benzoylhydrazino) carbonyl]benzyl}-3-bromobenzenesulfonamide) has 2.5-fold higher antagonistic activity than the lead compound 2 and represents our new lead compound. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.018

文献信息

• Systematic variation of the benzenesulfonamide part of the GluN2A selective NMDA receptor antagonist TCN-201
  作者：Sebastian L. Müller、Julian A. Schreiber、Dirk Schepmann、Nathalie Strutz-Seebohm、Guiscard Seebohm、Bernhard Wünsch

  DOI：10.1016/j.ejmech.2017.02.018

  日期：2017.3

  GluN2A subunit containing N-methyl-D-aspartate receptors (NMDARs) are highly involved in various physiological processes in the central nervous system, but also in some diseases, such as anxiety, depression and schizophrenia. However, the role of GluN2A subunit containing NMDARs in pathological processes is not exactly elucidated. In order to obtain potent and selective inhibitors of GluN2A subunit containing NMDARs, the selective negative allosteric modulator 2 was systematically modified at the benzenesulfonamide part. The activity of the test compounds was recorded in two electrode voltage clamp experiments using Xenopus laevis oocytes expressing exclusively NMDARs with GluN1a and GluN2A subunits. It was found that halogen atoms in 3-position of the benzenesulfonamide part result in high GluN2A antagonistic activity. With an IC50 value of 204 nM the 3-bromo derivative 5i (N-4-[(2-benzoylhydrazino) carbonyl]benzyl}-3-bromobenzenesulfonamide) has 2.5-fold higher antagonistic activity than the lead compound 2 and represents our new lead compound. (C) 2017 Elsevier Masson SAS. All rights reserved.