1-(4-aminosulfonylphenyl)-5-[1-(4-nitrooxybutyl)piperidin-4-yl]-3-trifluoromethyl-1H-pyrazole | 1219688-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-aminosulfonylphenyl)-5-[1-(4-nitrooxybutyl)piperidin-4-yl]-3-trifluoromethyl-1H-pyrazole
• 英文别名: 4-(4-(1-(4-sulfamoylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)piperidin-1-yl)butyl nitrate；4-[4-[2-(4-sulfamoylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]piperidin-1-yl]butyl nitrate
• CAS: 1219688-97-7
• 化学式: C₁₉H₂₄F₃N₅O₅S
• 分子量: 491.491
• InChiKey: ANYFNAGACQKDRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  145
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1-(4-aminosulfonylphenyl)-5-(piperidin-4-yl)-3-trifluoromethyl-1H-pyrazole 、 四溴丁基硝酸盐 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以11%的产率得到1-(4-aminosulfonylphenyl)-5-[1-(4-nitrooxybutyl)piperidin-4-yl]-3-trifluoromethyl-1H-pyrazole
  参考文献：
  名称：

  Celecoxib analogs possessing a N-(4-nitrooxybutyl)piperidin-4-yl or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridin-4-yl nitric oxide donor moiety: Synthesis, biological evaluation and nitric oxide release studies

  摘要：

  A new group of hybrid nitric oxide (NO) releasing anti-inflammatory (AI) coxib prodrugs (NO-coxibs) wherein the para-tolyl moiety present in celecoxib was replaced by a N-(4-nitrooxybutyl) piperidyl 15a-b, or N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl 17a-b, NO-donor moiety was synthesized. All compounds released a low amount of NO upon incubation with phosphate buffered saline (PBS) at pH 7.4 (2.4-5.8% range). In comparison, the percentage NO released was higher (3.1-8.4% range) when these nitrate prodrugs were incubated in the presence of L-cysteine. In vitro COX-1/COX-2 isozyme inhibition studies showed this group of compounds are moderately more potent, and hence selective, inhibitors of the COX-2 relative to the COX-1 enzyme. AI structure-activity relationship data acquired showed that compounds having a MeSO2 COX-2 pharmacophore exhibited superior AI activity compared to analogs having a H2NSO2 substituent. Compounds having a MeSO2 COX-2 pharmacophore in conjunction with a N-(4-nitrooxybutyl) piperidyl (ED50 = 132.4 mg/kg po), or a N-(4-nitrooxybutyl)-1,2,3,6-tetrahydropyridyl (ED50 = 118.4 mg/kg po), moiety exhibited an AI potency pro. le that is similar to aspirin (ED50 = 128.7 mg/kg po) but lower than ibuprofen (ED50 = 67.4 mg/kg po). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.014