2-(2-methoxy-4-nitrophenoxy)-1-(piperazin-1-yl)ethan-1-one

• 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: 2-(2-methoxy-4-nitrophenoxy)-1-(piperazin-1-yl)ethan-1-one
• 英文别名: 2-(2-Methoxy-4-nitrophenoxy)-1-piperazin-1-ylethanone
• 化学式: C₁₃H₁₇N₃O₅
• 分子量: 295.295
• InChiKey: BMTGEXVIOXIOJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  96.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-methoxy-4-nitrophenoxy)-1-(piperazin-1-yl)ethan-1-one 在 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 tert-butyl (2-(4-(2-(2-methoxy-4-(3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thioureido)phenoxy)acetyl)piperazin-1-yl)ethyl)carbamate
  参考文献：
  名称：

  Potent human glutaminyl cyclase inhibitors as potential anti-Alzheimer’s agents: Structure-activity relationship study of Arg-mimetic region

  摘要：

  Pyroglutamate-modified amyloid beta peptides (pGlu-A beta) are highly neurotoxic and promote the formation of amyloid plaques. The pGlu-A beta peptides are generated by glutaminyl cyclase (QC), and recent clinical studies indicate that QC represents an alternative therapeutic target to treat Alzheimer's disease (AD). We have previously developed a series of QC inhibitors with an extended pharmacophoric scaffold, termed the Arg-mimetic D-region. In the present study, we focused on the structure activity relationship (SAR) of analogues with modifications in the D-region and evaluated their biological activity. Most compounds in this series exhibited potent activity in vitro, and our SAR analysis and the molecular docking studies identified compound 202 as a potential candidate because it forms an additional hydrophobic interaction in the hQC active site. Overall, our study provides valuable insights into the Arg-mimetic pharmacophore that will guide the design of novel QC inhibitors as potential treatments for AD. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.01.015
• 作为产物：
  描述：

  2-(2-methoxy-4-nitrophenoxy)acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 2-(2-methoxy-4-nitrophenoxy)-1-(piperazin-1-yl)ethan-1-one
  参考文献：
  名称：

  Potent human glutaminyl cyclase inhibitors as potential anti-Alzheimer’s agents: Structure-activity relationship study of Arg-mimetic region

  摘要：

  Pyroglutamate-modified amyloid beta peptides (pGlu-A beta) are highly neurotoxic and promote the formation of amyloid plaques. The pGlu-A beta peptides are generated by glutaminyl cyclase (QC), and recent clinical studies indicate that QC represents an alternative therapeutic target to treat Alzheimer's disease (AD). We have previously developed a series of QC inhibitors with an extended pharmacophoric scaffold, termed the Arg-mimetic D-region. In the present study, we focused on the structure activity relationship (SAR) of analogues with modifications in the D-region and evaluated their biological activity. Most compounds in this series exhibited potent activity in vitro, and our SAR analysis and the molecular docking studies identified compound 202 as a potential candidate because it forms an additional hydrophobic interaction in the hQC active site. Overall, our study provides valuable insights into the Arg-mimetic pharmacophore that will guide the design of novel QC inhibitors as potential treatments for AD. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.01.015