N-Hydroxy-N-Methyl-4-((quinolin-2-yl)methoxy)phenylacetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-Hydroxy-N-Methyl-4-((quinolin-2-yl)methoxy)phenylacetamide
• 英文别名: N-Hydroxy-N-methyl-2-[4-(quinolin-2-ylmethoxy)-phenyl]-acetamide；N-hydroxy-N-methyl-2-[4-(quinolin-2-ylmethoxy)phenyl]acetamide
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: HIMOIVVELGFEPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  62.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对羟基苯乙酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 反应 37.0h， 生成 N-Hydroxy-N-Methyl-4-((quinolin-2-yl)methoxy)phenylacetamide
  参考文献：
  名称：

  Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from platelets and their in vivo effects on inflammation and anaphylaxis

  摘要：

  The synthesis of a series of novel substituted hydroxamates has been described along with their profile of inhibitory activity against 5-lipoxygenase, 12-lipoxygenase, and cyclooxygenase enzymes. The structure--activity relationship suggests that future molecules could be designed to specifically inhibit one or more of these enzymes since there were definite differences in structure--activity relationships for these different enzymes. A representative number of these compounds have been tested in vivo and found to possess potent oral activity in a systemic anaphylaxis model mediated by leukotrienes and topical activity in an arachidonic acid induced inflammation model. One of these molecules, compound 20, demonstrated that a leukotriene antagonist pharmacophore can be modified such that it contains both antagonist activity and 5-lipoxygenase inhibitory activity.

  DOI：

  10.1021/jm00128a027

文献信息

• Hydroxamates as modulators of arachidonic acid metabolic pathways
  申请人：USV PHARMACEUTICAL CORPORATION

  公开号：EP0196674A2

  公开（公告）日：1986-10-08

  This invention relates to new chemical compounds possessing valuable pharmaceutical activity, particularly as lipoxygenase inhibitors possessing anti-inflammatory and anti-allergic properties. The present new compounds are of the formula: and salts thereof; wherein R2 is H, lower alkyl, formyl or C2-C10 alkanoyl; R and R, are each independently hydrogen, lower cycloalkyl, fused cycloalkyl or lower alkyl-substituted fused cycloalkyl, lower alkyl, phenyl, naphthyl or a nitrogen, oxygen, or sulfur heterocyclic ring or heterocyclic-lower alkyl; Z, Z, and Z7 are each a chemical bond, or an alkylene chain or a mono- or di-substituted alkylene chain containing up to 6 carbon atoms in the principal chain and up to a total of about 10 carbon atoms, a lower cycloalkyl, a nitrogen oxygen, or sulfur heterocyclic ring or heterocyclic-lower alkyl, or a mono- or di-subsituted lower cycloalkyl or heterocyclic lower alkyl, and the substituents are hydrogen, lower alkyl, aryl, lower aralkyl, lower alkoxy, hydroxy, lower aralkoxy, aryloxy, carboxy, lower carbalkoxy, carbaryloxy, lower carbaralkoxy, amino, lower alkyl amino, amino loweralkyl, di-loweralkylamino or cyano; X and Y are each independently 0, S, CR3 R4 or a chemical bond; R3 and R4 are each independently H or lower alkyl; each R5 is hydrogen, aryl, lower alkarayl, formyl, nitro, cyano, amino, lower aminoalkyl, lower alkylamino, lower aralkylamino, halo, trihalo alkyl, carbamoyl or aroyl; n is an integer from 0-2; and n, is an integer from 1-2.

  本发明涉及具有宝贵药物活性的新化合物，特别是作为具有抗炎和抗过敏特性的脂氧合酶抑制剂。本发明的新化合物具有以下式子 及其盐类； 其中 R2 是 H、低级烷基、甲酰基或 C2-C10 烷酰基； R和R，各自独立地是氢、低级环烷基、融合环烷基或低级烷基取代的融合环烷基、低级烷基、苯基、萘基或氮、氧或硫杂环或杂环-低级烷基； Z、Z 和 Z7 各为化学键，或主链中最多含有 6 个碳原子且总共最多含有约 10 个碳原子的亚烷基链或单取代或二取代亚烷基链、低级环烷基、氮氧硫杂环或杂环低级烷基、或单取代或二取代的低级环烷基或杂环低级烷基，取代基为氢、低级烷基、芳基、低级芳烷基、低级烷氧基、羟基、低级芳烷氧基、芳氧基、羧基、低级碳烷氧基、碳酰氧基、低级碳烷氧基、氨基、低级烷基氨基、低级烷基氨基、二低级烷基氨基或氰基； X 和 Y 各自独立地为 0、S、CR3 R4 或化学键； R3 和 R4 各自独立地为 H 或低级烷基；R5 各自独立地为氢、芳基、低级烷基、甲酰基、硝基、氰基、氨基、低级氨基烷基、低级烷基氨基、低级芳基氨基、卤代、三卤代烷基、氨基甲酰基或芳基； n 是 0-2 之间的整数；和 n 是 1-2 之间的整数。
• HUANG, FU-CHIH;SHOUPE, T. SCOTT;LIN, CLARA J.;LEE, THOMAS D. Y.;CHAN, WAN+, J. MED. CHEM., 32,(1989) N, C. 1836-1842
  作者：HUANG, FU-CHIH、SHOUPE, T. SCOTT、LIN, CLARA J.、LEE, THOMAS D. Y.、CHAN, WAN+

  DOI：——

  日期：——
• US4792560A
  申请人：——

  公开号：US4792560A

  公开（公告）日：1988-12-20
• Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from platelets and their in vivo effects on inflammation and anaphylaxis
  作者：Fu Chih Huang、T. Scott Shoupe、Clara J. Lin、Thomas D. Y. Lee、Wan Kit Chan、Jenny Tan、Melvin Schnapper、John T. Suh、Robert J. Gordon

  DOI：10.1021/jm00128a027

  日期：1989.8

  The synthesis of a series of novel substituted hydroxamates has been described along with their profile of inhibitory activity against 5-lipoxygenase, 12-lipoxygenase, and cyclooxygenase enzymes. The structure--activity relationship suggests that future molecules could be designed to specifically inhibit one or more of these enzymes since there were definite differences in structure--activity relationships for these different enzymes. A representative number of these compounds have been tested in vivo and found to possess potent oral activity in a systemic anaphylaxis model mediated by leukotrienes and topical activity in an arachidonic acid induced inflammation model. One of these molecules, compound 20, demonstrated that a leukotriene antagonist pharmacophore can be modified such that it contains both antagonist activity and 5-lipoxygenase inhibitory activity.