N1-butyryl-3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N1-butyryl-3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide
• 英文别名: N-[3-fluoro-4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylbutanamide
• 化学式: C₂₁H₁₉F₄N₃O₄S
• 分子量: 485.459
• InChiKey: AHRORBZPGUSFAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (Z)-4,4,4-Trifluoro-3-hydroxy-1-(4-methoxy-phenyl)-but-2-en-1-one 在 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 36.0h， 生成 N1-butyryl-3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore:  Preparation of Sodium Salt for Injectable Formulation^†

  摘要：

  A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.

  DOI：

  10.1021/jm020563g

文献信息

• Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore:  Preparation of Sodium Salt for Injectable Formulation^†
  作者：Manojit Pal、Manjula Madan、Srinivas Padakanti、Vijaya R. Pattabiraman、Srinivas Kalleda、Akhila Vanguri、Ramesh Mullangi、N. V. S. Rao Mamidi、Seshagiri R. Casturi、Alpeshkumar Malde、B. Gopalakrishnan、Koteswar R. Yeleswarapu

  DOI：10.1021/jm020563g

  日期：2003.9.1

  A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.