4-(2-amino-4-bromo-phenyl)-1-tert-butoxycarbonyl-piperazine | 474329-58-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(2-amino-4-bromo-phenyl)-1-tert-butoxycarbonyl-piperazine
• 英文别名: Tert-butyl 4-(2-amino-4-bromophenyl)piperazine-1-carboxylate
• CAS: 474329-58-3
• 化学式: C₁₅H₂₂BrN₃O₂
• 分子量: 356.263
• InChiKey: TUEBPXXMKKULPM-UHFFFAOYSA-N

物化性质

• 沸点：
  465.1±45.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  58.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-amino-4-bromo-phenyl)-1-tert-butoxycarbonyl-piperazine 在 dppf-Pd(II) 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 potassium acetate 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 84.5h， 生成 tert-butyl 4-{2-[(2-oxo-2H-chromene-3-)amido]-4-phenylphenyl}piperazine-1-carboxylate
  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：

  2,5-二溴硝基苯 在 sodium dithionite 、 sodium carbonate 、 三乙胺 作用下， 以 甲醇 、 水 、 异丙醇 为溶剂， 反应 24.0h， 生成 4-(2-amino-4-bromo-phenyl)-1-tert-butoxycarbonyl-piperazine
  参考文献：
  名称：

  作为潜在抗阿尔茨海默病药物的亚氨基-2H-铬烯衍生物：设计、合成、生物学评价和计算机研究

  摘要：

  合理设计和合成了一系列新的亚氨基-2 H-色烯衍生物作为抗阿尔茨海默病的新型多功能药物。一组苯基亚氨基-2 H-色烯以及新合成的亚氨基色烯衍生物被评估为 BACE1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 抑制剂。结果表明，在亚氨基色素组中，带有氟苄基部分的10c是最有效的 BACE1 抑制剂，IC 50值为 6.31 μM。体外抗胆碱能活性表明，带有苄基侧基的化合物10a是 AChE（30 μM 时抑制百分比=24.4）和 BuChE（IC 50= 3.3 微米）。还进行了化合物10a针对 BuChE的动力学分析，并显示出混合型抑制模式。神经保护评估显示，化合物11b是一种具有羟乙基部分的苯基亚氨基-2 H-色烯衍生物，在 25 μM 时对 Aβ 诱导的 PC12 神经元细胞损伤提供 32.3% 的保护。此外，针对 BACE1 和 BuChE 的最有效化合物的对接和模拟研究证实了实验结果。

  DOI：

  10.1002/cbdv.202100599

文献信息

• Inhibitors of bace
  申请人：——

  公开号：US20030095958A1

  公开（公告）日：2003-05-22

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.

  本发明涉及天冬氨酸蛋白酶抑制剂，特别是BACE。本发明还涉及其组合物和方法，用于在哺乳动物中抑制BACE活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。
• 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.
• INHIBITORS OF BACE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1389194A2

  公开（公告）日：2004-02-18
• AZABICYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1476448A2

  公开（公告）日：2004-11-17