1-(4-methanesulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyridin-2-one)]-3-trifluoromethyl-1H-pyrazole | 1131479-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-methanesulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyridin-2-one)]-3-trifluoromethyl-1H-pyrazole
• 英文别名: 1-(Difluoromethyl)-4-[2-(4-methylsulfonylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]pyridin-2-one
• CAS: 1131479-22-5
• 化学式: C₁₇H₁₂F₅N₃O₃S
• 分子量: 433.359
• InChiKey: OHIAVULGDFAQDO-UHFFFAOYSA-N

物化性质

• 熔点：
  200-202 °C
• 沸点：
  593.2±50.0 °C(predicted)
• 密度：
  1.52±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  80.6
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氟磺酰基二氟乙酸 、 1-(4-methanesulfonylphenyl)-5-(2-chloropyridin-4-yl)-3-trifluoromethyl-1H-pyrazole 在 碳酸氢钠 作用下， 以46%的产率得到1-(4-methanesulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyridin-2-one)]-3-trifluoromethyl-1H-pyrazole
  参考文献：
  名称：

  Synthesis of Celecoxib Analogues Possessing a N-Difluoromethyl-1,2-dihydropyrid-2-one 5-Lipoxygenase Pharmacophore: Biological Evaluation as Dual Inhibitors of Cyclooxygenases and 5-Lipoxygenase with Anti-Inflammatory Activity

  摘要：

  A novel class of 1-(4-methanesulfonylphenyl and 4-aminosulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyrid-2-one)]-3-trifluoromethyl-1H-pyrazole hybrid cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LOX) inhibitory anti-inflammatory agents was designed. Replacement of the tolyl ring present in celecoxib by the N-difluoromethyl-1,2-dihydropyrid-2-one moiety provided compounds showing dual selective COX-2/5-LOX inhibitory activities. 1-(4-Aminosulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyrid-2-one)]-3-trifluoromethyl-1H-pyrazole exhibited good anti-inflammatory (AI) activity (ED50 = 27.7 mg/kg po) that compares favorably with the reference drugs celecoxib ED50 = 10.8 mg/kg po) and ibuprofen (ED50 = 67.4 mg/kg po). The N-difluoromethyl-1,2-dihydropyridin-2-one moiety provides a novel 5-LOX pharmacophore for the design of cyclic hydroxamic mimetics for exploitation in the development of COX-2/5-LOX inhibitory AI drugs.

  DOI：

  10.1021/jm8015188