2-(3,4-dimethoxyphenyl)-N-(3-imidazol-1-ylpropyl)acetamide

• 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-(3,4-dimethoxyphenyl)-N-(3-imidazol-1-ylpropyl)acetamide
• 化学式: C₁₆H₂₁N₃O₃
• 分子量: 303.361
• InChiKey: KRUXLUSHXJPIMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.65
• 重原子数：
  22.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  65.38
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(3,4-dimethoxyphenyl)-N-(3-imidazol-1-ylpropyl)acetamide 在 劳森试剂 作用下， 以 1,4-二氧六环 为溶剂， 反应 8.0h， 以0.14 g的产率得到N-(3-(1H-imidazol-1-yl)propyl)-2-(3,4-dimethoxyphenyl)ethanethioamide
  参考文献：
  名称：

  The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship

  摘要：

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

  DOI：

  10.1021/jm050756e
• 作为产物：
  描述：

  1-(3-氨基丙基)咪唑 、 (3,4-二甲氧基苯基)乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(3,4-dimethoxyphenyl)-N-(3-imidazol-1-ylpropyl)acetamide
  参考文献：
  名称：

  The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship

  摘要：

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

  DOI：

  10.1021/jm050756e

文献信息

• US7897633B2
  申请人：——

  公开号：US7897633B2

  公开（公告）日：2011-03-01
• The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship
  作者：Mirko Buchholz、Ulrich Heiser、Stephan Schilling、André J. Niestroj、Katrin Zunkel、Hans-Ulrich Demuth

  DOI：10.1021/jm050756e

  日期：2006.1.1

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.