methyl 1-(3-hydroxymethyl-4-sulfamoylphenyl)-5-(4-methoxyphenyl)-1H-3-pyrazolecarboxylate | 869899-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 1-(3-hydroxymethyl-4-sulfamoylphenyl)-5-(4-methoxyphenyl)-1H-3-pyrazolecarboxylate
• CAS: 869899-08-1
• 化学式: C₁₉H₁₉N₃O₆S
• 分子量: 417.442
• InChiKey: DWAWMCFMZPFBIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.47
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  133.74
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl 1-(3-hydroxymethyl-4-sulfamoylphenyl)-5-(4-methoxyphenyl)-1H-3-pyrazolecarboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以68%的产率得到1-(3-Hydroxymethyl-4-sulfamoyl-phenyl)-5-(4-methoxy-phenyl)-1H-pyrazole-3-carboxylic acid
  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：

  对甲氧基苯乙酮 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 methyl 1-(3-hydroxymethyl-4-sulfamoylphenyl)-5-(4-methoxyphenyl)-1H-3-pyrazolecarboxylate
  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