tert-butyl 4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate | 1470189-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate
• 英文别名: t-Butyl 4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1h-pyrazol-5-yl)piperidine-1-carboxylate；tert-butyl 4-[5-methyl-2-(4-methylsulfonylphenyl)pyrazol-3-yl]piperidine-1-carboxylate
• CAS: 1470189-61-7
• 化学式: C₂₁H₂₉N₃O₄S
• 分子量: 419.545
• InChiKey: FNUUBWLONLKZLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 7.33h， 生成 (4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1H-pyrazol-5-yl)piperidin-1-yl)(4-methoxyphenyl)methanone
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 4-(1-(4(sulphanilamide)phenyl)-3-(methyl)-1H-pyrazol-5-yl)dine urea and N-acyl derivatives as a soluble epoxide hydrolase inhibitors

  摘要：

  A series of novel sEH inhibitors containing a N-substituted piperidine ring [N-urea (8a-i) (9a-l) and amide derivatives (6a-l) (7a-l)] with pyrazole (a five-membered polar heterocycle) as a pharmacophore lead for sEH inhibition have been designed, synthesized and evaluated as novel analogues to reduce blood pressure elevation and inflammatory roles by acting as sEH inhibitors. The synthesized compound shows varying degree of selectivity towards the sEH enzymes. Particularly compounds 9g and 8h emerged as the most potent sEH inhibitor displaying IC50 values of 0.224 +/- A 0.014 and 0.220 +/- A 0.03 mu M for in vitro sEH inhibition. Molecular docking studies of the designed sEH dual inhibitors are performed using 1ZD5 for sEH as the targeted proteins and which revealed H-bond interactions similar to AUDA. Structure-activity relationships provided useful insights in these classes of compounds and paved the way to design novel analogues with increased potency.Schematic representation of proposed sEH Inhibitors.

  DOI：

  10.1007/s00044-013-0817-8
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 21.0h， 生成 tert-butyl 4-(3-methyl-1-(4-(methylsulphonyl)phenyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 4-(1-(4(sulphanilamide)phenyl)-3-(methyl)-1H-pyrazol-5-yl)dine urea and N-acyl derivatives as a soluble epoxide hydrolase inhibitors

  摘要：

  A series of novel sEH inhibitors containing a N-substituted piperidine ring [N-urea (8a-i) (9a-l) and amide derivatives (6a-l) (7a-l)] with pyrazole (a five-membered polar heterocycle) as a pharmacophore lead for sEH inhibition have been designed, synthesized and evaluated as novel analogues to reduce blood pressure elevation and inflammatory roles by acting as sEH inhibitors. The synthesized compound shows varying degree of selectivity towards the sEH enzymes. Particularly compounds 9g and 8h emerged as the most potent sEH inhibitor displaying IC50 values of 0.224 +/- A 0.014 and 0.220 +/- A 0.03 mu M for in vitro sEH inhibition. Molecular docking studies of the designed sEH dual inhibitors are performed using 1ZD5 for sEH as the targeted proteins and which revealed H-bond interactions similar to AUDA. Structure-activity relationships provided useful insights in these classes of compounds and paved the way to design novel analogues with increased potency.Schematic representation of proposed sEH Inhibitors.

  DOI：

  10.1007/s00044-013-0817-8