4-{4-bromo-2-[(naphthalene-1-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester | 474329-59-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-{4-bromo-2-[(naphthalene-1-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-[4-bromo-2-(naphthalene-1-carbonylamino)phenyl]piperazine-1-carboxylate
• CAS: 474329-59-4
• 化学式: C₂₆H₂₈BrN₃O₃
• 分子量: 510.431
• InChiKey: YJJFMJAXEJFWKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-{4-bromo-2-[(naphthalene-1-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester 、 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36%的产率得到Tert-butyl 4-[2-(naphthalene-1-carbonylamino)-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 potassium dihydrogenphosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 52.0h， 生成 4-{4-bromo-2-[(naphthalene-1-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester
  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

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.
• INHIBITORS OF BACE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1389194A2

  公开（公告）日：2004-02-18
• [EN] INHIBITORS OF BACE<br/>[FR] INHIBITEURS DE BACE
  申请人：VERTEX PHARMA

  公开号：WO2002088101A2

  公开（公告）日：2002-11-07

  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.
• 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.