N-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-oxo-2H-chromene-3-carboxamide | 883908-09-6

• 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-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-oxo-2H-chromene-3-carboxamide
• 英文别名: N-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-oxochromene-3-carboxamide
• CAS: 883908-09-6
• 化学式: C₂₇H₂₄BrN₃O₃
• 分子量: 518.41
• InChiKey: RVLRVRRSGYQIIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-oxo-2H-chromene-3-carboxamide 、 苯硼酸 在 dppf-Pd(II) 1,1'-双(二苯基膦)二茂铁 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 72.0h， 以51%的产率得到N-[2-(4-benzylpiperazin-1-yl)-5-phenylphenyl]-2-oxo-2H-chromene-3-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：

  2,5-二溴硝基苯 在 吡啶 、 potassium dihydrogenphosphate 、 TEA 、 锌 、 三氯氧磷 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 20.0h， 生成 N-[2-(4-benzylpiperazin-1-yl)-5-bromophenyl]-2-oxo-2H-chromene-3-carboxamide
  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