1-(3-methoxyphenyl)-2-(1-methylhydrazino)ethanol hydrogen fumarate | 387355-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(3-methoxyphenyl)-2-(1-methylhydrazino)ethanol hydrogen fumarate
• 英文别名: 2-[amino(methyl)amino]-1-(3-methoxyphenyl)ethanol;(E)-but-2-enedioic acid
• CAS: 387355-81-9
• 化学式: C₄H₄O₄*C₁₀H₁₆N₂O₂
• 分子量: 312.323
• InChiKey: PEFUEXCKUPFFOC-WLHGVMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.25
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-methylamino-N-nitroso-1-(m-methoxyphenyl)-1-ethanol 、 富马酸 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 生成 1-(3-methoxyphenyl)-2-(1-methylhydrazino)ethanol hydrogen fumarate
  参考文献：
  名称：

  Synthesis, in Vitro Activity, and Three-Dimensional Quantitative Structure−Activity Relationship of Novel Hydrazine Inhibitors of Human Vascular Adhesion Protein-1

  摘要：

  Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those seen in the crystal structures to bind. Combining the data from molecular dynamics simulations, docking, and in vitro measurements, the three-dimensional quantitative structure-activity relationship (3D QSAR) models for VAP-1 (q(LOO)(2): 0.636; r(2:) 0.828) and MAOs (q(LOO)(2): 0.749, r(2): 0.840) were built and employed in the development of selective VAP-1 inhibitors.

  DOI：

  10.1021/jm100337z

文献信息

• Synthesis, in Vitro Activity, and Three-Dimensional Quantitative Structure−Activity Relationship of Novel Hydrazine Inhibitors of Human Vascular Adhesion Protein-1
  作者：Elisa M. Nurminen、Marjo Pihlavisto、László Lázár、Zsolt Szakonyi、Ulla Pentikäinen、Ferenc Fülöp、Olli T. Pentikäinen

  DOI：10.1021/jm100337z

  日期：2010.9.9

  Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those seen in the crystal structures to bind. Combining the data from molecular dynamics simulations, docking, and in vitro measurements, the three-dimensional quantitative structure-activity relationship (3D QSAR) models for VAP-1 (q(LOO)(2): 0.636; r(2:) 0.828) and MAOs (q(LOO)(2): 0.749, r(2): 0.840) were built and employed in the development of selective VAP-1 inhibitors.