5-[4-(O2-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole | 1245272-98-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[4-(O2-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole
• 英文别名: 1-acetyloxyethoxyimino-oxido-[4-[2-(4-sulfamoylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]phenyl]azanium
• CAS: 1245272-98-3
• 化学式: C₂₀H₁₈F₃N₅O₆S
• 分子量: 513.454
• InChiKey: IEMHWLGLOUDENU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  151.94
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  1-溴乙基乙酸酯 、 5-[4-(O2-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以23%的产率得到5-[4-(O2-(1-acetoxyethyl)diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole
  参考文献：
  名称：

  Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Synthesis, biological evaluation and nitric oxide release studies

  摘要：

  A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O-2-methyl and O-2-acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O-2-methyl and O-2-acetoxyethyl compounds was higher (18.0-37.8% of the theoretical maximal release of one molecule of NO/molecule of the parent compound) upon incubation in the presence of rat serum, relative to incubation with phosphate buffer saline (PBS) at pH 7.4 (3.8-11.6% range). All compounds exhibited weak inhibition of the COX-1 isozyme (IC50 = 5.8-17.0 mu M range) in conjunction with weak or modest inhibition of the COX-2 isozyme (IC50 = 1.6-14.4 mu M range). The most potent AI agent 5-[4-(O-2-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole exhibited a potency that was about fourfold and twofold greater than that observed for the respective reference drugs aspirin and ibuprofen. These studies indicate that use of a cupferron template constitutes a plausible drug design approach targeted toward the development of AI drugs that do not cause gastric irritation, or elevate blood pressure and induce platelet aggregation that have been associated with the use of some selective COX-2 inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.022