5-Acetyl-2,6-dimethyl-4-nitropyridazin-3-one | 121910-73-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 5-Acetyl-2,6-dimethyl-4-nitropyridazin-3-one
• CAS: 121910-73-4
• 化学式: C₈H₉N₃O₄
• 分子量: 211.177
• InChiKey: RPGHEGKXAUFRMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-Acetyl-2,6-dimethyl-4-nitropyridazin-3-one 在 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 4-ethylamino-5-(1-hydroxyethyl)-2,6-dimethylpyridazin-3(2H)-one
  参考文献：
  名称：

  作为口服活性抗伤害药的4-氨基-5-取代-3（2H）-哒嗪酮：合成及作用机理的研究。

  摘要：

  合成了许多4-氨基-5-乙烯基吡啶酮酮和4-氨基-5-杂环吡啶酮酮，并测试了它们的镇痛活性。以3-20 mg kg-1 po的剂量测试的许多这些化合物均显示出良好的抗伤害感受活性，相对于对照而言，减少了超过50％的扭伤次数。化合物16c，19a，20a和28是该系列中最有效的化合物，因为它们能够以3 mg kg-1 po的剂量诱导有效的镇痛作用。如旋转仪测试所示，在镇痛剂量下，没有一种活性化合物引起正常行为的任何可见变化。作用机理的研究表明，用α2-拮抗剂育亨宾预处理可以完全阻止由活性化合物引起的镇痛作用，这表明α2-肾上腺素能受体的参与。

  DOI：

  10.1021/jm070161e
• 作为产物：
  描述：

  3,4,6-trimethylisoxazolo<3,4-d>pyridazin-7(6H)-one 在 ammonium cerium(IV) nitrate 、 硝酸 、 溶剂黄146 作用下， 生成 5-Acetyl-2,6-dimethyl-4-nitropyridazin-3-one
  参考文献：
  名称：

  作为有效抗伤害药的4-氨基-5-乙烯基-3（2H）-哒嗪酮及其类似物：合成，SAR和作用机理的初步研究。

  摘要：

  合成了一系列的4-氨基-5-乙烯基-3（2H）-哒嗪酮及其类似物，并在小鼠腹部收缩模型中评估了它们的抗伤害作用。几种新化合物的ED（50）值在6-20mg / kg / sc范围内，并证明能够完全保护所有处理过的动物免受30 mg / kg / sc的有害刺激的影响。SAR研究证实，二嗪系统第4位的氨基或取代的氨基官能团和第5位的乙烯基具有重要的作用。

  DOI：

  10.1016/j.bmc.2007.05.035

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.
• Phenylpiperazinylalkylamino Substituted Pyridazinones as Potent α₁ Adrenoceptor Antagonists
  作者：Daniela Barlocco、Giorgio Cignarella、Vittorio Dal Piaz、M. Paola Giovannoni、Pier G. De Benedetti、Francesca Fanelli、Federica Montesano、Elena Poggesi、Amedeo Leonardi

  DOI：10.1021/jm0009336

  日期：2001.7.1

  QSAR models have been used for designing a series of compounds characterized by a N-phenylpiperazinylalkylamino moiety linked to substituted pyridazinones, which have been synthesized. Measurements of the binding affinities of the new compounds toward the alpha (1a)-, alpha (1b)-, and alpha (1d)-AR cloned subtypes as well as the 5-HT1A receptor have been done validating, at least in part, the estimations of the theoretical models. This study provides insight into the structure activity relationships of the alpha (1)-ARs ligands and their alpha (1)-AR/5-HT1A selectivity.
• Piaz, Vittorio Dal; Ciciani, Giovanna; Turco, Giovanni, Synthesis, 1989, # 3, p. 213 - 214
  作者：Piaz, Vittorio Dal、Ciciani, Giovanna、Turco, Giovanni

  DOI：——

  日期：——
• PIAZ, VITTORIO DAL;CICIANI, GIOVANNA;TUREO, GIOVANNI, SYNTHESIS,(1989) N, C. 213-215
  作者：PIAZ, VITTORIO DAL、CICIANI, GIOVANNA、TUREO, GIOVANNI

  DOI：——

  日期：——
• PISZ, V. D.;CICIANI, G.;GIOVANNONI, M. P.;TURCO, G., HETEROCYCLES, 29,(1989) N, C. 1595-1600
  作者：PISZ, V. D.、CICIANI, G.、GIOVANNONI, M. P.、TURCO, G.

  DOI：——

  日期：——