N-甲基-3-(4-硝基-1-萘基)丙烯酰氧肟酸 | 105847-25-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: N-甲基-3-(4-硝基-1-萘基)丙烯酰氧肟酸
• 英文名称: N-methyl-3-(4-nitro-1-naphthyl)acrylohydroxamic acid
• 英文别名: N-Hydroxy-N-methyl-3-(4-nitro-naphthalen-1-yl)-acrylamide；(E)-N-hydroxy-N-methyl-3-(4-nitronaphthalen-1-yl)prop-2-enamide
• CAS: 105847-25-4
• 化学式: C₁₄H₁₂N₂O₄
• 分子量: 272.26
• InChiKey: SZMYCUROFONYBK-VQHVLOKHSA-N

物化性质

• 沸点：
  462.9±47.0 °C(Predicted)
• 密度：
  1.397±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基羟胺 、 3t-(4-nitro-naphthyl-(1))-acrylic acid 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 生成 N-甲基-3-(4-硝基-1-萘基)丙烯酰氧肟酸
  参考文献：
  名称：

  Hydroxamic acid inhibitors of 5-lipoxygenase: quantitative structure-activity relationships

  摘要：

  An evaluation of the quantitative structure-activity relationships (QSAR) for more than 100 hydroxamic acids revealed that the primary physicochemical feature influencing the in vitro 5-lipoxygenase inhibitory potencies of these compounds is the hydrophobicity of the molecule. A significant correlation was observed between the octanol-water partition coefficient of the substituent attached to the carbonyl of the hydroxamate and in vitro inhibitory activity. This correlation held for hydroxamic acids of diverse structure and with potencies spanning 4 orders of magnitude. Although the hydrophobicity may be packaged in a variety of structural ways and still correlate with potency, the QSAR study revealed two major exceptions. Specifically, the hydrophobicity of portions of compounds in the immediate vicinity of the hydroxamic acid functionality does not appear to contribute to increased inhibition and the hydrophobicity of fragments beyond approximately 12 A from the hydroxamate do not influence potency. The QSAR study also demonstrated that inhibitory activity was enhanced when there was an alkyl group on the hydroxamate nitrogen, when electron-withdrawing substituents were present and when the hydroxamate was conjugated to an aromatic system. These observations provide a simple description of the lipoxygenase-hydroxamic acid binding site.

  DOI：

  10.1021/jm00165a017

文献信息

• Lipoxygenase inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0199153A2

  公开（公告）日：1986-10-29

  Compounds of the formula where X is selected from hydrogen, C1 to C22 alkyl or alkenyl, or an electron withdrawing group; n =0 or 1 and m=0, 1, 2 or 3; but n and m are not 0 simultaneously; R1 and R2 independently are hydrogen, C1 to C6 alkyl, an electron withdrawing group, or R4; R3 is H, C1 to C6 alkyl or cycloalkyl, or R4; and R4 independently at each occurrence, has the formula where Y is hydrogen or an electron withdrawing group; and wherein M is a pharmaceutically acceptable cation, are potent inhibitors of lipoxygenase enzymes.

  式中X选自氢、C1至C22烷基或烯基或电子僻取基团；n＝0或1和m＝0、1、2或3；但n和m不同时为0；R1和R2独立地为氢、C1至C6烷基、电子僻取基团或R4； R3 是 H、C1 至 C6 烷基或环烷基，或 R4；以及 R4 在每次出现时独立地具有如下式 Y 是氢或取电子基团；其中 M 是药学上可接受的阳离子，它们是脂氧合酶的强效抑制剂。
• US4608390A
  申请人：——

  公开号：US4608390A

  公开（公告）日：1986-08-26
• Hydroxamic acid inhibitors of 5-lipoxygenase: quantitative structure-activity relationships
  作者：James B. Summers、Ki H. Kim、Hormoz Mazdiyasni、James H. Holms、James D. Ratajczyk、Andrew O. Stewart、Richard D. Dyer、George W. Carter

  DOI：10.1021/jm00165a017

  日期：1990.3

  An evaluation of the quantitative structure-activity relationships (QSAR) for more than 100 hydroxamic acids revealed that the primary physicochemical feature influencing the in vitro 5-lipoxygenase inhibitory potencies of these compounds is the hydrophobicity of the molecule. A significant correlation was observed between the octanol-water partition coefficient of the substituent attached to the carbonyl of the hydroxamate and in vitro inhibitory activity. This correlation held for hydroxamic acids of diverse structure and with potencies spanning 4 orders of magnitude. Although the hydrophobicity may be packaged in a variety of structural ways and still correlate with potency, the QSAR study revealed two major exceptions. Specifically, the hydrophobicity of portions of compounds in the immediate vicinity of the hydroxamic acid functionality does not appear to contribute to increased inhibition and the hydrophobicity of fragments beyond approximately 12 A from the hydroxamate do not influence potency. The QSAR study also demonstrated that inhibitory activity was enhanced when there was an alkyl group on the hydroxamate nitrogen, when electron-withdrawing substituents were present and when the hydroxamate was conjugated to an aromatic system. These observations provide a simple description of the lipoxygenase-hydroxamic acid binding site.