3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one | 526200-64-6

• 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: 3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one
• 英文别名: 3-Methylisoxazolo[3,4-d]pyridazin-7-ol；3-methyl-6H-[1,2]oxazolo[3,4-d]pyridazin-7-one
• CAS: 526200-64-6
• 化学式: C₆H₅N₃O₂
• 分子量: 151.125
• InChiKey: ZGDXZKBOGYMVMD-UHFFFAOYSA-N

物化性质

• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one 、 1-(3-bromopropyl)-4-(p-tolyl)piperazine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以72%的产率得到3-methyl-6-[3-(4-p-tolylpiperazin-1-yl)propyl]isoxazolo[3,4-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain

  摘要：

  A number of pyridazinone derivatives bearing all arylpiperazinylalkyl chain were synthesized and tested icv in it model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED50 = 3.5 mu g, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting it significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.

  DOI：

  10.1021/jm900458r
• 作为产物：
  描述：

  Ethyl 4-formyl-5-methyl-1,2-oxazole-3-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以60%的产率得到3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain

  摘要：

  A number of pyridazinone derivatives bearing all arylpiperazinylalkyl chain were synthesized and tested icv in it model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED50 = 3.5 mu g, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting it significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.

  DOI：

  10.1021/jm900458r

文献信息

• Pyridazinone Derivatives
  申请人：Bacon Edward R.

  公开号：US20100280007A1

  公开（公告）日：2010-11-04

  The present invention is directed to novel pyridizinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition.

  本发明涉及新型吡啶酮衍生物，可介导酶活性。特别是，这些化合物可能在治疗与组胺H3受体活性相关的疾病或病态方面具有有效性，包括神经退行性疾病、睡眠/觉醒障碍、注意力缺陷多动障碍和认知等。