2-(3-fluoro-5-methylphenyl)-3-(4-methylsulfonylphenyl)-5-(trifluoromethyl)-4H-imidazol-5-ol | 1026751-60-9

• 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: 2-(3-fluoro-5-methylphenyl)-3-(4-methylsulfonylphenyl)-5-(trifluoromethyl)-4H-imidazol-5-ol
• CAS: 1026751-60-9
• 化学式: C₁₈H₁₆F₄N₂O₃S
• 分子量: 416.396
• InChiKey: LELQADJIEMLUHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-fluoro-5-methylphenyl)-3-(4-methylsulfonylphenyl)-5-(trifluoromethyl)-4H-imidazol-5-ol 在 三乙基硼 、 正丁基氯化镁 、 对甲苯磺酸 、 hydroxylamine-O-sulfonic acid 作用下， 以 甲苯 为溶剂， 反应 72.0h， 生成 4-[2-(3-fluoro-5-methylphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225
• 作为产物：
  描述：

  3-氟--5-甲基苯甲醛 在 吡啶 、 盐酸羟胺 、 三甲基铝 、 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 44.75h， 生成 2-(3-fluoro-5-methylphenyl)-3-(4-methylsulfonylphenyl)-5-(trifluoromethyl)-4H-imidazol-5-ol
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225

文献信息

• 1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents
  作者：Ish K. Khanna、Richard M. Weier、Yi Yu、Xiang D. Xu、Francis J. Koszyk、Paul W. Collins、Carol M. Koboldt、Amy W. Veenhuizen、William E. Perkins、Jacquelen J. Casler、Jaime L. Masferrer、Yan Y. Zhang、Susan A. Gregory、Karen Seibert、Peter C. Isakson

  DOI：10.1021/jm9700225

  日期：1997.5.1

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.