4,4,4-Trifluoro-1-(3-methyl-4-methylsulfanyl-phenyl)-butane-1,3-dione | 922728-88-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,4,4-Trifluoro-1-(3-methyl-4-methylsulfanyl-phenyl)-butane-1,3-dione
• CAS: 922728-88-9
• 化学式: C₁₂H₁₁F₃O₂S
• 分子量: 276.279
• InChiKey: QJMPVXQTRJJXEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.42
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  34.14
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4,4,4-Trifluoro-1-(3-methyl-4-methylsulfanyl-phenyl)-butane-1,3-dione 在 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-Hydroxymethyl-4-[5-(4-methanesulfinyl-3-methyl-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-benzenesulfonamide
  参考文献：
  名称：

  Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore

  摘要：

  Diverse analogs of 1,5-diarylpyrazoles having 3-hydroxymethyl-4-sulfamoyl (SO2NH2)/methyl sulfonyl (SO2Me)-pheny group at N-1 were synthesized and evaluated for their in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The SAR study mainly involved the variations at positions C-3, C-5 and N-1 of the pyrazole ring. Several small hydrophobic groups at/around position-4 of C-5 phenyl, viz. 3,4-dimethylphenyl analog 9, 3-methyl-4-methylsulfanylphenyl analog 14 and 2,3-dihydrobenzo[b]thiophenyl analog 17, exhibited impressive COX-2 inhibitory potency. In general, the sulfonamide analogues with a CHF2 at C-3 were found to be more potent than those having a CF3 group. The three dimensional quantitative structure activity relationship comprising comparative molecular field analysis (3D-QSAR-CoMFA) afforded the models with high predictivity which further validated the acceptance of hydroxymethyl (CH2OH) group in the hydrophilic pocket of the COX-2 enzyme. (c) 2005 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.03.016
• 作为产物：
  描述：

  三氟乙酸乙酯 、 3-methyl-4-methylthioacetophenone 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4,4,4-Trifluoro-1-(3-methyl-4-methylsulfanyl-phenyl)-butane-1,3-dione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)

  摘要：

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

  DOI：

  10.1021/jm960803q