4-benzyloxy-N-[4'-(trifluoromethyl)biphenyl-4-yl]-1,2,5-oxadiazole-3-carboxamide | 1364791-76-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-benzyloxy-N-[4'-(trifluoromethyl)biphenyl-4-yl]-1,2,5-oxadiazole-3-carboxamide
• CAS: 1364791-76-3
• 化学式: C₂₃H₁₆F₃N₃O₃
• 分子量: 439.394
• InChiKey: CHHZPJVOACSKBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.59
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  77.25
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-benzyloxy-N-[4'-(trifluoromethyl)biphenyl-4-yl]-1,2,5-oxadiazole-3-carboxamide 在 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 为溶剂， 以55%的产率得到4-hydroxy-N-[4'-trifluoromethylbiphenyl-4-yl]-1,2,5-oxadiazole-3-carboxamide
  参考文献：
  名称：

  New inhibitors of dihydroorotate dehydrogenase (DHODH) based on the 4-hydroxy-1,2,5-oxadiazol-3-yl (hydroxyfurazanyl) scaffold

  摘要：

  Based on some structural analogies with leflunomide and brequinar, two well-known inhibitors of dihydroorotate dehydrogenase (DHODH), a new series of products was designed, by joining the substituted biphenyl moiety to the 4-hydroxy-1,25-oxadiazol-3-yl scaffold through an amide bridge. The compounds were studied for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. The activity was found to be closely dependent on the substitution pattern at the biphenyl system; the most potent products were those bearing two or four fluorine atoms at the phenyl adjacent to the oxadiazole ring. A molecular modeling study suggested that these structures might have a bre-quinar-like binding mode. The greater potency of fluorinated analogs may depend partly on enhanced interactions with the hydrophobic ubiquinone channel, and partly on the role of fluorine in stabilizing the putative bioactive conformation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.038
• 作为产物：
  描述：

  4-(benzyloxy)-1,2,5-oxadiazole-3-carboxylic acid 、 4-三氟甲基联苯-4-胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以71%的产率得到4-benzyloxy-N-[4'-(trifluoromethyl)biphenyl-4-yl]-1,2,5-oxadiazole-3-carboxamide
  参考文献：
  名称：

  New inhibitors of dihydroorotate dehydrogenase (DHODH) based on the 4-hydroxy-1,2,5-oxadiazol-3-yl (hydroxyfurazanyl) scaffold

  摘要：

  Based on some structural analogies with leflunomide and brequinar, two well-known inhibitors of dihydroorotate dehydrogenase (DHODH), a new series of products was designed, by joining the substituted biphenyl moiety to the 4-hydroxy-1,25-oxadiazol-3-yl scaffold through an amide bridge. The compounds were studied for their DHODH inhibitory activity on rat liver mitochondrial/microsomal membranes. The activity was found to be closely dependent on the substitution pattern at the biphenyl system; the most potent products were those bearing two or four fluorine atoms at the phenyl adjacent to the oxadiazole ring. A molecular modeling study suggested that these structures might have a bre-quinar-like binding mode. The greater potency of fluorinated analogs may depend partly on enhanced interactions with the hydrophobic ubiquinone channel, and partly on the role of fluorine in stabilizing the putative bioactive conformation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.12.038