5-acetyl-4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one | 1192490-69-9

• 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: 5-acetyl-4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one
• 英文别名: 5-Acetyl-4-amino-6-methyl-2-[3-[4-(4-methylphenyl)piperazin-1-yl]propyl]pyridazin-3-one
• CAS: 1192490-69-9
• 化学式: C₂₁H₂₉N₅O₂
• 分子量: 383.494
• InChiKey: ROXIDJWARBKXCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-acetyl-4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以88%的产率得到4-amino-5-(1-hydroxyethyl)-6-methyl-2-[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
• 作为产物：
  描述：

  3,4-二甲基-6H-异噁唑并[3,4-d]哒嗪-7-酮 在 palladium 10% on activated carbon 、 甲酸铵 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 5-acetyl-4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one
  参考文献：
  名称：

  Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents

  摘要：

  A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl) propyl]-5-vinylpyridazin-3 (2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with alpha(2)-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.043

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.
• Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents
  作者：Claudia Vergelli、Giovanna Ciciani、Agostino Cilibrizzi、Letizia Crocetti、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Gabriella Guerrini、Antonella Iacovone、Maria Paola Giovannoni

  DOI：10.1016/j.bmc.2015.08.043

  日期：2015.10

  A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl) propyl]-5-vinylpyridazin-3 (2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with alpha(2)-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds. (C) 2015 Elsevier Ltd. All rights reserved.