2-(3-cyano-4-propoxyphenyl)-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(3-cyano-4-propoxyphenyl)-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acid
• 英文别名: 2-(3-Cyano-4-propoxyphenyl)-3-hydroxy-5-methylimidazole-4-carboxylic acid；2-(3-cyano-4-propoxyphenyl)-3-hydroxy-5-methylimidazole-4-carboxylic acid
• 化学式: C₁₅H₁₅N₃O₄
• 分子量: 301.302
• InChiKey: BICRHTCNBYZSRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-溴-4-羟基苯甲醛 在 ammonium acetate 、 水 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 2-(3-cyano-4-propoxyphenyl)-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives as non-purine xanthine oxidase inhibitors

  摘要：

  Xanthine oxidase is a key enzyme that catalyses hypoxanthine and xanthine to uric acid, whose overproduction leads to the gout-causing hyperuricemia. In this study, a series of 1-hydroxy/methoxy-4-methy1-2-phenyl-1H-imidazole-5-carboxylic acid derivatives (4a-4k and 6a-6k) was synthesized and evaluated for their inhibitory potency against xanthine oxidase. The 1-hydroxyl substituted derivatives 4a-4k showed excellent inhibitory potency with IC50 values ranging from 0.003 mu M to 1.2 mu M, with compounds 4d (IC50 = 0.003 mu M), 4e (IC50 = 0.003 FM), and 4f (IC50 = 0.006 mu M) manifesting the most potent xanthine oxidase inhibitory potency that were comparable with that of Febuxostat (IC50 = 0.01 410). Lineweaver-Burk plot analysis revealed that representative compound 4f acted as a mixed-type inhibitor for xanthine oxidase. The basis of significant inhibition of xanthine oxidase by 4f was rationalized by its molecular docking into the active site of xanthine dehydrogenase. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.056