3,4-Dimethyl-6-[2-(4-p-tolyl-piperazin-1-yl)-ethyl]-6H-isoxazolo[3,4-d]pyridazin-7-one | 681829-10-7

• 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: 3,4-Dimethyl-6-[2-(4-p-tolyl-piperazin-1-yl)-ethyl]-6H-isoxazolo[3,4-d]pyridazin-7-one
• CAS: 681829-10-7
• 化学式: C₂₀H₂₅N₅O₂
• 分子量: 367.451
• InChiKey: PSZZTZABOKCXID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  67.4
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  3,4-Dimethyl-6-[2-(4-p-tolyl-piperazin-1-yl)-ethyl]-6H-isoxazolo[3,4-d]pyridazin-7-one 在 palladium on activated charcoal 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以80%的产率得到5-Acetyl-4-amino-6-methyl-2-[2-(4-p-tolyl-piperazin-1-yl)-ethyl]-2H-pyridazin-3-one
  参考文献：
  名称：

  4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups and related compounds: synthesis and antinociceptive activity

  摘要：

  A series of 4-amino-3(2H)-pyridazinones substituted at position 2 with arylpiperazinylalkyl groups and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Preliminary SARs studies were performed. Several of the novel compounds dosed at 100 mg/kg s.c. significantly reduced the number of writhes induced by the noxious stimulus. Compound 12e showed 100% inhibition of writhes and was able to protect all the treated animals from the effect of the chemical stimulus. Subsequent dose-response studies revealed 12e to be almost 40-fold more potent than the structurally related Emorfazone.

  DOI：

  10.1016/s0014-827x(03)00162-9
• 作为产物：
  描述：

  3,4-二甲基-6H-异噁唑并[3,4-d]哒嗪-7-酮 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3,4-Dimethyl-6-[2-(4-p-tolyl-piperazin-1-yl)-ethyl]-6H-isoxazolo[3,4-d]pyridazin-7-one
  参考文献：
  名称：

  4-Amino-3(2H)-pyridazinones bearing arylpiperazinylalkyl groups and related compounds: synthesis and antinociceptive activity

  摘要：

  A series of 4-amino-3(2H)-pyridazinones substituted at position 2 with arylpiperazinylalkyl groups and analogues were synthesized and their antinociceptive effect was evaluated in the mouse abdominal constriction model. Preliminary SARs studies were performed. Several of the novel compounds dosed at 100 mg/kg s.c. significantly reduced the number of writhes induced by the noxious stimulus. Compound 12e showed 100% inhibition of writhes and was able to protect all the treated animals from the effect of the chemical stimulus. Subsequent dose-response studies revealed 12e to be almost 40-fold more potent than the structurally related Emorfazone.

  DOI：

  10.1016/s0014-827x(03)00162-9

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.