3-methoxy-4-(2-(4-phenylpiperazin-1-yl)ethoxy)aniline | 96238-80-1

• 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: 3-methoxy-4-(2-(4-phenylpiperazin-1-yl)ethoxy)aniline
• 英文别名: 3-Methoxy-4-[2-(4-phenyl-1-piperazinyl)ethoxy]benzenamine；3-methoxy-4-[2-(4-phenylpiperazin-1-yl)ethoxy]aniline
• CAS: 96238-80-1
• 化学式: C₁₉H₂₅N₃O₂
• 分子量: 327.426
• InChiKey: QUBNPERGMCWQIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  50.96
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(5-methyl-1H-imidazol-1-yl)propan-1-amine 、 3-methoxy-4-(2-(4-phenylpiperazin-1-yl)ethoxy)aniline 、 N,N'-硫羰基二咪唑 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到1-(3-methoxy-4-(2-(4-phenylpiperazin-1-yl)ethoxy)phenyl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
  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：

  1-(2-(2-methoxy-4-nitrophenoxy)ethyl)-4-phenylpiperazine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以92%的产率得到3-methoxy-4-(2-(4-phenylpiperazin-1-yl)ethoxy)aniline
  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