5-(3-bromopropyl)-3-methyl-7-phenylisoxazolo[4,5-d]pyridazin-4(5H)-one | 502135-12-8

• 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: 5-(3-bromopropyl)-3-methyl-7-phenylisoxazolo[4,5-d]pyridazin-4(5H)-one
• 英文别名: 5-(3-Bromopropyl)-3-methyl-7-phenyl-[1,2]oxazolo[4,5-d]pyridazin-4-one
• CAS: 502135-12-8
• 化学式: C₁₅H₁₄BrN₃O₂
• 分子量: 348.199
• InChiKey: RFFZVPVTOOJDPO-UHFFFAOYSA-N

物化性质

• 沸点：
  513.8±60.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  1-(3-氯苯基)哌嗪 、 5-(3-bromopropyl)-3-methyl-7-phenylisoxazolo[4,5-d]pyridazin-4(5H)-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以85%的产率得到5-{3-[4-(3-Chloro-phenyl)-piperazin-1-yl]-propyl}-3-methyl-7-phenyl-5H-isoxazolo[4,5-d]pyridazin-4-one
  参考文献：
  名称：

  [(3-Chlorophenyl)piperazinylpropyl]pyridazinones and Analogues as Potent Antinociceptive Agents

  摘要：

  A number of [(3-chlorophenyl)piperazinylpropyl]pyridazinones and the corresponding isoxazolo-pyridazinones, showing the arylpiperazinyl substructure present in very potent antinociceptive agents reported in the literature, were synthesized and tested for their analgesic activity. The investigated compounds showed antinociceptive properties in the mouse hot-plate test (thermal nociceptive stimulus) after systemic administration with an efficacy similar to that exerted by morphine. The increase of the pain threshold induced by the compounds labeled 5a, 7, 8, and 11 was prevented by reserpine, suggesting the involvement of the noradrenergic and/or serotoninergic system in their mechanism of action. Among them, 7 and 11 showed the highest analgesic potency and efficacy together with a good ratio (133 and 200, respectively) of the minimal nontoxic dose (MNTD) to the minimal analgesic dose (MAD). Furthermore, they were also active after icv administration and in the presence of a chemical, painful stimulus (abdominal constriction test).

  DOI：

  10.1021/jm021057u
• 作为产物：
  描述：

  3-Methyl-7-phenyl-5H-isoxazolo[4,5-d]pyridazin-4-one 、 1,3-二溴丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以72%的产率得到5-(3-bromopropyl)-3-methyl-7-phenylisoxazolo[4,5-d]pyridazin-4(5H)-one
  参考文献：
  名称：

  [(3-Chlorophenyl)piperazinylpropyl]pyridazinones and Analogues as Potent Antinociceptive Agents

  摘要：

  A number of [(3-chlorophenyl)piperazinylpropyl]pyridazinones and the corresponding isoxazolo-pyridazinones, showing the arylpiperazinyl substructure present in very potent antinociceptive agents reported in the literature, were synthesized and tested for their analgesic activity. The investigated compounds showed antinociceptive properties in the mouse hot-plate test (thermal nociceptive stimulus) after systemic administration with an efficacy similar to that exerted by morphine. The increase of the pain threshold induced by the compounds labeled 5a, 7, 8, and 11 was prevented by reserpine, suggesting the involvement of the noradrenergic and/or serotoninergic system in their mechanism of action. Among them, 7 and 11 showed the highest analgesic potency and efficacy together with a good ratio (133 and 200, respectively) of the minimal nontoxic dose (MNTD) to the minimal analgesic dose (MAD). Furthermore, they were also active after icv administration and in the presence of a chemical, painful stimulus (abdominal constriction test).

  DOI：

  10.1021/jm021057u

文献信息

• Arylpiperazinylalkylpyridazinones and Analogues as Potent and Orally Active Antinociceptive Agents:  Synthesis and Studies on Mechanism of Action
  作者：Nicoletta Cesari、Claudio Biancalani、Claudia Vergelli、Vittorio Dal Piaz、Alessia Graziano、Pierfrancesco Biagini、Carla Ghelardini、Nicoletta Galeotti、Maria Paola Giovannoni

  DOI：10.1021/jm060743g

  日期：2006.12.1

  arylpiperazinylalkylpyridazinones structurally related to the previously described lead A (5-[4-(3-chlorophenyl)piperazin-1-yl]-propyl}-3-methyl-7-phenylisossazolo[4,5-d] pyridazin-4-(5H)-one) were synthesized and tested for their analgesic activity. Many of the tested molecules, at the dose of 20 mg kg-1 p.o., showed high antinociceptive activity, in particular, compounds 5a, 11c, 15a, 21 and 22, which were

  在结构上与先前描述的铅A（5-[4-（3-氯苯基）哌嗪-1-基]-丙基} -3-甲基-7-苯基异s唑并[4,5-d]哒嗪-合成4-（5H）-一）并测试其镇痛活性。许多受试分子的剂量为20 mg kg-1 po，表现出很高的抗伤害感受活性，尤其是化合物5a，11c，15a，21和22，能够将腹部收缩的数量减少50多种％在扭体测试中。铅A的药理研究使我们阐明了该化合物的作用机理，表明它通过抑制去甲肾上腺素的再摄取而发挥了镇痛作用。用α2-拮抗剂育亨宾预处理可以完全防止某些最有趣的新分子的抗伤害感受，