3-硝基-4-(4-苄基-1-哌嗪)溴苯 | 883522-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 3-硝基-4-(4-苄基-1-哌嗪)溴苯
• 英文名称: 1-benzyl-4-(4-bromo-2-nitro-phenyl)-piperazine
• 英文别名: 1-Benzyl-4-(4-bromo-2-nitrophenyl)piperazine
• CAS: 883522-59-6
• 化学式: C₁₇H₁₈BrN₃O₂
• mdl: MFCD06656553
• 分子量: 376.253
• InChiKey: YCSTXMIJSXRRHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  483.3±45.0 °C(Predicted)
• 密度：
  1.452±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.294
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  3-硝基-4-(4-苄基-1-哌嗪)溴苯 在 palladium on activated charcoal 、 dppf-Pd(II) 1,1'-双(二苯基膦)二茂铁 、 potassium dihydrogenphosphate 、 potassium acetate 、 ammonium formate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 116.0h， 生成 N-(2-{4-[5-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)pentyl]piperazin-1-yl}-5-phenylphenyl)naphthalene-1-carboxamide
  参考文献：
  名称：

  Naphthyl and Coumarinyl Biarylpiperazine Derivatives as Highly Potent Human β-Secretase Inhibitors. Design, Synthesis, and Enzymatic BACE-1 and Cell Assays

  摘要：

  Twenty novel beta-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinyl series were designed for their potential use in Alzheimer's disease therapy. Enzymatic and cell-based assays have been carried out. The biological results clearly demonstrate that specific substituents located at the N-4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between 40 and 70 nM). Variable temperature NMR and modeling studies are consistent with the obtained biological data, since these studies confirmed that introduction at the N-4-position of the piperazine ring allows productive interactions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitory activity. These results are of particular interest since some of the new analogues belonging to the naphthyl series are almost one log more active than the best inhibitor of the similar family recently reported.

  DOI：

  10.1021/jm0602864
• 作为产物：
  描述：

  1-苄基哌嗪 、 2,5-二溴硝基苯 在 TEA 作用下， 以 异丙醇 为溶剂， 反应 12.0h， 生成 3-硝基-4-(4-苄基-1-哌嗪)溴苯
  参考文献：
  名称：

  BACE-1 inhibitory activities of new substituted phenyl-piperazine coupled to various heterocycles: Chromene, coumarin and quinoline

  摘要：

  The protease beta-secretase plays a central role in the synthesis of pathogenic amyloid-beta in Alzheimer's disease. Here, we report a new series of analogues based on the phenyl-piperazine scaffold coupled to various heterocyclic moieties, which demonstrate improved inhibitory activities on BACE-1 (FRET assay) compared to already known naphthyl counterparts. The obtained results suggest further structural modifications to access to more potent BACE-1 inhibitors. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.12.064

文献信息

• BACE-1 inhibitory activities of new substituted phenyl-piperazine coupled to various heterocycles: Chromene, coumarin and quinoline
  作者：Cédrik Garino、Nicolas Pietrancosta、Younes Laras、Vincent Moret、Amandine Rolland、Gilles Quéléver、Jean-Louis Kraus

  DOI：10.1016/j.bmcl.2005.12.064

  日期：2006.4

  The protease beta-secretase plays a central role in the synthesis of pathogenic amyloid-beta in Alzheimer's disease. Here, we report a new series of analogues based on the phenyl-piperazine scaffold coupled to various heterocyclic moieties, which demonstrate improved inhibitory activities on BACE-1 (FRET assay) compared to already known naphthyl counterparts. The obtained results suggest further structural modifications to access to more potent BACE-1 inhibitors. (C) 2006 Elsevier Ltd. All rights reserved.
• Phenylimino-2 H -chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)
  作者：Najmeh Edraki、Omidreza Firuzi、Alireza Foroumadi、Ramin Miri、Armin Madadkar-Sobhani、Mehdi Khoshneviszadeh、Abbas Shafiee

  DOI：10.1016/j.bmc.2013.01.064

  日期：2013.4

  The inhibition of beta secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable p-p stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1-S'1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC50 value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on A beta production in N2a-APPswe cells at 5 and 10 mu M. These compounds might be considered as promising BACE1 inhibitory agents that could lower A beta production in AD. (C) 2013 Elsevier Ltd. All rights reserved.
• Naphthyl and Coumarinyl Biarylpiperazine Derivatives as Highly Potent Human β-Secretase Inhibitors. Design, Synthesis, and Enzymatic BACE-1 and Cell Assays
  作者：Cédrik Garino、Taisuke Tomita、Nicolas Pietrancosta、Younes Laras、Roselyne Rosas、Gaëtan Herbette、Bernard Maigret、Gilles Quéléver、Takeshi Iwatsubo、Jean-Louis Kraus

  DOI：10.1021/jm0602864

  日期：2006.7.1

  Twenty novel beta-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinyl series were designed for their potential use in Alzheimer's disease therapy. Enzymatic and cell-based assays have been carried out. The biological results clearly demonstrate that specific substituents located at the N-4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between 40 and 70 nM). Variable temperature NMR and modeling studies are consistent with the obtained biological data, since these studies confirmed that introduction at the N-4-position of the piperazine ring allows productive interactions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitory activity. These results are of particular interest since some of the new analogues belonging to the naphthyl series are almost one log more active than the best inhibitor of the similar family recently reported.