6-Oxo-2-(3-oxo-1,3,4,5,6,7-hexahydro-indazol-2-yl)-1,6-dihydro-pyrimidine-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-Oxo-2-(3-oxo-1,3,4,5,6,7-hexahydro-indazol-2-yl)-1,6-dihydro-pyrimidine-5-carboxylic acid
• 英文别名: 4-Hydroxy-2-(3-oxo-1,3,4,5,6,7-hexahydro-2H-indazol-2-yl)-5-pyrimidinecarboxylic acid；6-oxo-2-(3-oxo-4,5,6,7-tetrahydro-1H-indazol-2-yl)-1H-pyrimidine-5-carboxylic acid
• 化学式: C₁₂H₁₂N₄O₄
• 分子量: 276.252
• InChiKey: NIBDQHFWTFEATL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氧代-1,3,4,5,6,7-六氢-2H-吲唑-2-羧酰胺 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 6-Oxo-2-(3-oxo-1,3,4,5,6,7-hexahydro-indazol-2-yl)-1,6-dihydro-pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones

  摘要：

  In our reinvestigation of the cyclocondensation reaction of aminoguanidine bicarbonate 1 with 2-acetylbutyrolactone 2 and ethyl cyclohexanone-2-carboxylate 6, we have obtained the respective 1-amidino-3-pyrazolin-5-one derivative 3 and the 2-amidino-1,2,4,5,6,7-hexahydro-3H-indazol-3-one 7. These intermediates were utilized for the synthesis of two novel series of 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones. Selected analogs from both series (15 compounds) were evaluated for their antiinflammatory activity in an acute and subacute model of inflammation. The analgesic and antipyretic activity of the target compounds were also evaluated. A structure-activity relationship (SAR) comparative study indicated that some compounds from both series exhibited excellent antiinflammatory activity, together with good analgesic and antipyretic activity and were found to be more potent than the reference drugs at a dose of 50 mg/kg, po. In consideration of the efficacy of the compounds in these assays, the 5-phenyl derivative 18 from the 1-(pyrimidin-2-yl)pyrazolinone series, the 5-butyl and 5-phenyl derivatives 26, 27 from the 2-(pyrimidin-2-yl)indazolone series were further studied at graded doses for their acute toxicity (ALD(50)) and ulcerogenic activity and were shown to have a large safety margin (ALD(50) > 4.0 g/kg, po) and devoid of ulcerogenic potentialities when administered orally at a dose of 300 mg/kg. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80002-0

文献信息

• Nonsteroidal antiinflammatory agents - Part 1: Antiinflammatory, analgesic and antipyretic activity of some new 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones
  作者：El-Sayed A.M. Badawey、Ibrahim M. El-Ashmawey

  DOI：10.1016/s0223-5234(98)80002-0

  日期：1998.6

  In our reinvestigation of the cyclocondensation reaction of aminoguanidine bicarbonate 1 with 2-acetylbutyrolactone 2 and ethyl cyclohexanone-2-carboxylate 6, we have obtained the respective 1-amidino-3-pyrazolin-5-one derivative 3 and the 2-amidino-1,2,4,5,6,7-hexahydro-3H-indazol-3-one 7. These intermediates were utilized for the synthesis of two novel series of 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)-1,2,4,5,6,7-hexahydro-3H-indazol-3-ones. Selected analogs from both series (15 compounds) were evaluated for their antiinflammatory activity in an acute and subacute model of inflammation. The analgesic and antipyretic activity of the target compounds were also evaluated. A structure-activity relationship (SAR) comparative study indicated that some compounds from both series exhibited excellent antiinflammatory activity, together with good analgesic and antipyretic activity and were found to be more potent than the reference drugs at a dose of 50 mg/kg, po. In consideration of the efficacy of the compounds in these assays, the 5-phenyl derivative 18 from the 1-(pyrimidin-2-yl)pyrazolinone series, the 5-butyl and 5-phenyl derivatives 26, 27 from the 2-(pyrimidin-2-yl)indazolone series were further studied at graded doses for their acute toxicity (ALD(50)) and ulcerogenic activity and were shown to have a large safety margin (ALD(50) > 4.0 g/kg, po) and devoid of ulcerogenic potentialities when administered orally at a dose of 300 mg/kg. (C) Elsevier, Paris.