2-methylamino-N-nitroso-1-(m-methoxyphenyl)-1-ethanol | 387356-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-methylamino-N-nitroso-1-(m-methoxyphenyl)-1-ethanol
• 英文别名: N-[2-hydroxy-2-(3-methoxyphenyl)ethyl]-N-methylnitrous amide
• CAS: 387356-02-7
• 化学式: C₁₀H₁₄N₂O₃
• 分子量: 210.233
• InChiKey: NAJQKMSIRYOANC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methylamino-N-nitroso-1-(m-methoxyphenyl)-1-ethanol 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 N-methyl-2-methoxy-2-(m-methoxyphenyl)-N-nitroso-ethylamine
  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
• 作为产物：
  描述：

  1-(3-甲氧基苯基)-2-(甲基氨) 乙醇 在 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 生成 2-methylamino-N-nitroso-1-(m-methoxyphenyl)-1-ethanol
  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

• Inhibitors of copper-containing amine oxidases
  申请人：Biotie Therapies Corp.

  公开号：US20020173521A1

  公开（公告）日：2002-11-21

  The present invention is directed to hydrazono compounds that function as inhibitors of copper-containg amine oxidases commonly known as semicarbazide-sensitive amine oxidases (SSAO), including the human SSAO known as Vascular Adhesion Protein-1 (VAP-1). These SSAO inhibitors have therapeutic utility as drugs to treat conditions and diseases including, but not limited to, a number of inflammatory conditions and diseases (in particular chronic inflammatory conditions such as chronic arthritis, inflammatory bowel diseases, and chronic skin dermatoses), diseases related to carbohydrate metabolism and to aberrations in adipocyte differentiation or function and smooth muscle cell function, and vascular diseases. The compounds have the general formula: 1 or a pharmaceutically acceptable solvate, hydrate, or salt thereof, wherein R 1 to R 8 and X are as defined herein.

  本发明涉及一种作为铜含量胺氧化酶抑制剂的肼酰基化合物，这些胺氧化酶通常被称为半卡巴嗪敏感胺氧化酶（SSAO），包括人类已知的血管粘附蛋白-1（VAP-1）胺氧化酶。这些SSAO抑制剂在治疗条件和疾病方面具有治疗效用，包括但不限于许多炎症性疾病（特别是慢性炎症性疾病，如慢性关节炎、炎症性肠病和慢性皮肤皮肤病）、与碳水化合物代谢和脂肪细胞分化或功能异常以及平滑肌细胞功能以及血管疾病相关的疾病。这些化合物具有一般公式：1或其药学上可接受的溶剂、水合物或盐，其中R1至R8和X如本文所定义。
• US6624202B2
  申请人：——

  公开号：US6624202B2

  公开（公告）日：2003-09-23
• 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.