6-Butyl-3,4-dimethyl-[1,2]oxazolo[3,4-d]pyridazin-7-one | 910315-67-2

• 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-Butyl-3,4-dimethyl-[1,2]oxazolo[3,4-d]pyridazin-7-one
• CAS: 910315-67-2
• 化学式: C₁₁H₁₅N₃O₂
• 分子量: 221.259
• InChiKey: KJTKIGKQFVJKFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-Butyl-3,4-dimethyl-[1,2]oxazolo[3,4-d]pyridazin-7-one 在 palladium on activated charcoal ammonium formate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以79%的产率得到5-acetyl-4-amino-2-n-butyl-6-methylpyridazin-3(2H)-one
  参考文献：
  名称：

  作为口服活性抗伤害药的4-氨基-5-取代-3（2H）-哒嗪酮：合成及作用机理的研究。

  摘要：

  合成了许多4-氨基-5-乙烯基吡啶酮酮和4-氨基-5-杂环吡啶酮酮，并测试了它们的镇痛活性。以3-20 mg kg-1 po的剂量测试的许多这些化合物均显示出良好的抗伤害感受活性，相对于对照而言，减少了超过50％的扭伤次数。化合物16c，19a，20a和28是该系列中最有效的化合物，因为它们能够以3 mg kg-1 po的剂量诱导有效的镇痛作用。如旋转仪测试所示，在镇痛剂量下，没有一种活性化合物引起正常行为的任何可见变化。作用机理的研究表明，用α2-拮抗剂育亨宾预处理可以完全阻止由活性化合物引起的镇痛作用，这表明α2-肾上腺素能受体的参与。

  DOI：

  10.1021/jm070161e
• 作为产物：
  描述：

  3,4-二甲基-6H-异噁唑并[3,4-d]哒嗪-7-酮 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到6-Butyl-3,4-dimethyl-[1,2]oxazolo[3,4-d]pyridazin-7-one
  参考文献：
  名称：

  Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction

  摘要：

  Pyrazolo[1', 5': 1,6] pyrimido[4,5-d] pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 = 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.

  DOI：

  10.1021/jm060265+

文献信息

• 4-Amino-5-substituted-3(2<i>H</i>)-pyridazinones as Orally Active Antinociceptive Agents:  Synthesis and Studies on the Mechanism of Action
  作者：Maria Paola Giovannoni、Nicoletta Cesari、Claudia Vergelli、Alessia Graziano、Claudio Biancalani、Pierfrancesco Biagini、Carla Ghelardini、Elisa Vivoli、Vittorio Dal Piaz

  DOI：10.1021/jm070161e

  日期：2007.8.1

  doses of 3-20 mg kg-1 po, showed good antinociceptive activity, reducing by more than 50% the number of writhes with respect to controls. Compounds 16c, 19a, 20a, and 28 were the most potent of the series because they were able to induce a potent antinociceptive effect at a dose of 3 mg kg-1 po. None of the active compounds at the analgesic dose provoked any visible change in normal behavior, as demonstrated

  合成了许多4-氨基-5-乙烯基吡啶酮酮和4-氨基-5-杂环吡啶酮酮，并测试了它们的镇痛活性。以3-20 mg kg-1 po的剂量测试的许多这些化合物均显示出良好的抗伤害感受活性，相对于对照而言，减少了超过50％的扭伤次数。化合物16c，19a，20a和28是该系列中最有效的化合物，因为它们能够以3 mg kg-1 po的剂量诱导有效的镇痛作用。如旋转仪测试所示，在镇痛剂量下，没有一种活性化合物引起正常行为的任何可见变化。作用机理的研究表明，用α2-拮抗剂育亨宾预处理可以完全阻止由活性化合物引起的镇痛作用，这表明α2-肾上腺素能受体的参与。
• Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction
  作者：Maria Paola Giovannoni、Claudia Vergelli、Claudio Biancalani、Nicoletta Cesari、Alessia Graziano、Pierfrancesco Biagini、Jordi Gracia、Amadeu Gavaldà、Vittorio Dal Piaz

  DOI：10.1021/jm060265+

  日期：2006.8.1

  Pyrazolo[1', 5': 1,6] pyrimido[4,5-d] pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 = 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.