4-amino-5-(1-hydroxyethyl)-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one | 1192490-40-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-amino-5-(1-hydroxyethyl)-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one
• 英文别名: 4-Amino-5-(1-hydroxyethyl)-6-methyl-2-[3-[4-(4-methylphenyl)piperazin-1-yl]-3-oxopropyl]pyridazin-3-one
• CAS: 1192490-40-6
• 化学式: C₂₁H₂₉N₅O₃
• 分子量: 399.493
• InChiKey: QZOSFEUTNOMZJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-amino-5-(1-hydroxyethyl)-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one 在 polyphosphoric acid 作用下， 反应 3.0h， 以50%的产率得到4-amino-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-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：

  5-acetyl-4-amino-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以90%的产率得到4-amino-5-(1-hydroxyethyl)-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-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

• Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain
  作者：Claudio Biancalani、Maria Paola Giovannoni、Stefano Pieretti、Nicoletta Cesari、Alessia Graziano、Claudia Vergelli、Agostino Cilibrizzi、Amalia Di Gianuario、Mariantonella Colucci、Giorgina Mangano、Beatrice Garrone、Lorenzo Polenzani、Vittorio Dal Piaz

  DOI：10.1021/jm900458r

  日期：2009.12.10

  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.