4-hydrazino-phthalazin-1(2H)-one | 14161-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-hydrazino-phthalazin-1(2H)-one
• 英文别名: 4-hydrazinophthalazine-1(2H)-one；4-hydrazinylphthalazin-1(2H)-one；4-hydrazinophthalazin-1-one；4-hydrazino-2H-phthalazin-1-one；4-Hydrazino-2H-phthalazin-1-on；4-Hydrazino-1(2H)-phthalazinon；4-hydrazinyl-2H-phthalazin-1-one
• CAS: 14161-35-4
• 化学式: C₈H₈N₄O
• mdl: MFCD06654121
• 分子量: 176.178
• InChiKey: GSXANHNUSCYGEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-hydrazino-phthalazin-1(2H)-one 在 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one
  参考文献：
  名称：

  3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-a]phthalazines and Analogues:  High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Binding Selectivity over α1

  摘要：

  Studies with our screening lead 5 and the literature compound 6 led to the identification of 6-benzyloxy-3-(4-methoxy)phenyl-1,2,4-triazolo[3,4-a]phthalazine 8 as a ligand with binding selectivity for the gamma-aminobutyric acid-A (GABA-A) alpha3- and alpha5-containing receptor subtypes over the GABA-A alpha1 subtype (K-i: alpha2 = 850 nM, alpha3 = 170 nM, alpha5 = 72 nM, alpha1 = 1400 nM). Early optimization studies identified the close analogue 10 (Ki: alpha2 = 16 nM, alpha3 = 41 nM, alpha5 = 38 nM, alpha1 = 280 nM) as a suitable lead for further study. High-affinity ligands were identified by replacing the 6-benzyloxy group of compound 10 with 2-pyridylmethoxy (compound 29), but binding selectivity was not enhanced (K-i: alpha2 = 1.7 nM, alpha3 = 0.71 nM, alpha5 = 0.33 nM, alpha1 = 2.7 nM). Furthermore, on evaluation in xenopus oocytes,(22) 29 was discovered to be a weak to moderate inverse agonist at all four receptor subtypes (alpha1, -7%; alpha2, -5%; alpha3, -16%; alpha5, -5%). Replacement of the 3-phenyl group of 29 with alternatives led to reduced affinity, and smaller 3-substituents led to reduced efficacy. Methyl substitution of the benzo-fused ring of 29 at the 7-, 8-, and 10-positions resulted in increased efficacy although selectivity was abolished. Increased efficacy and retention of selectivity for alpha3 over alpha1 was achieved with the 7,8,9,10-tetrahydro-(7,10-ethano)-phthalazine 62. Compound 62 is currently one of the most binding selective GABA-A alpha3-benzodiazepine-site partial agonists known, and although its selectivity is limited, its good pharmacokinetic profile in the rat (33% oral bioavailability after a 3 mg/kg dose, reaching a peak plasma concentration of 179 ng/mL; half-life of I h) made it a useful pharmacological tool to explore the effect of a GABA-A alpha2/alpha3 agonist in vivo.

  DOI：

  10.1021/jm031020p
• 作为产物：
  描述：

  1,4-二氯酞嗪 在 一水合肼 作用下， 生成 4-hydrazino-phthalazin-1(2H)-one
  参考文献：
  名称：

  Kumada et al., Yakugaku Kenkyu, 1958, vol. 30, p. 635,640

  摘要：

  DOI：

文献信息

• Synthesis and evaluation of the anticonvulsant activities of 2,3-dihydrophthalazine-1,4-dione derivatives
  作者：Xiang-Jun Liu、Hong-Jian Zhang、Zhe-Shan Quan

  DOI：10.1007/s00044-017-1896-8

  日期：2017.9

  (Tox). The results showed that 5-(3-(trifluoromethyl)benzyl)-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one (6e) had the most potent anticonvulsant activity with an ED50 value of 6.8 mg/kg and protective index (PI = TD50/ED50) value of 11.5 (i.p.); its anticonvulsant activity was found to be stronger than that of the lead compound and the standard drug carbamazepine. In particular, compound 6e protected

  合成了一系列带有三唑（6a – y）和其他杂环取代基（8a – b，9a – b，10a – b，12a – b和14a – b）的2,3-二氢邻苯二甲酰1,4-二酮衍生物。及其结构的特征在于使用IR，1 H-NMR，13 C-NMR和MS。使用最大电击测试评估其抗惊厥活性，并使用旋转脚架神经毒性测试（Tox）评估其神经毒性。结果表明5-（3-（三氟甲基）苄基）-[1,2,4]三唑[3,4-a ] phthalazin-6（5 H）-one（6e）具有最强的抗惊厥活性，ED 50值为6.8 mg / kg，保护指数（PI = TD 50 / ED 50）为11.5（ip）；发现其抗惊厥活性强于先导化合物和标准药物卡马西平。尤其是，化合物6e可以防止戊四唑和双瓜氨酸引起的癫痫发作。
• Usnic acid derivatives as tau-aggregation and neuroinflammation inhibitors
  作者：Cun-Jian Shi、Wan Peng、Jin-Hua Zhao、Hua-Li Yang、Lai-Liang Qu、Cheng Wang、Ling-Yi Kong、Xiao-Bing Wang

  DOI：10.1016/j.ejmech.2019.111961

  日期：2020.2

  diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6

  tau蛋白聚集的积累在神经退行性疾病（例如阿尔茨海默氏病（AD））中起着至关重要的作用。无法控制的神经炎症和tau病理形成一个恶性循环，进一步加剧了AD进展。在此，我们报道了松香酸衍生物的合成及其对tau聚集和神经炎症抑制作用的评估。首先通过ThT荧光测定法筛选了衍生物对六肽AcPHF6的自纤化的抑制活性。使用圆二色性和透射电子显微镜观察，化合物30对AcPHF6自纤颤表现出最强的抑制活性。进一步证实化合物30通过肝素诱导的机制抑制全长2N4R tau蛋白的聚集。此外，我们研究了化合物30的抗炎活性，结果表明与尿酸钠相比，它减少了LPS刺激的小鼠小胶质细胞BV2细胞中的NO释放。更重要的是，有30种药物对冈田酸诱导的大鼠记忆力损伤表现出明显的保护作用。因此，30是一种新型的tau聚集和神经炎症抑制剂，代表了AD的潜在治疗候选药物。
• Synthesis, IR-, NMR- and X-ray investigations on some novel N-hetaryl-dihydro-pyrazolyl ferrocenes. Study on ferrocenes, part 16
  作者：Veronika Kudar、Virág Zsoldos-Mády、Kálmán Simon、Antal Csámpai、Pál Sohár

  DOI：10.1016/j.jorganchem.2005.05.045

  日期：2005.9

  Cyclocondensation of 1-aryl-3-ferrocenyl-2-propen-1-ones (1) with hetaryl hydrazines resulted in N-hetaryl-3-aryl-5-ferrocenyl pyrazolines (3, 4). The analogous 3-aryl-1-ferrocenyl-2-propen-1-ones (5) gave the isomeric N-hetaryl-5-aryl-3-ferrocenyl-pyrazolines (6, 10), but in lower yield. The reaction of aryl-chalcones (7) with 4-hydrazino-phthalazinone led to 3,5-bis-aryl-N-hetaryl-pyrazolines (8)

  的1-芳基-3-二茂铁基-2-丙烯-1-酮（环缩合1）与杂芳基肼导致Ñ -hetaryl -3-芳基-5-吡唑啉二茂铁（3，4）。类似的3-芳基-1-二茂铁基-2-丙烯-1-酮（5），得到同分异构的Ñ -hetaryl -5-芳基-3-二茂铁基吡唑啉（6，10），但在较低的产率。芳基-查耳酮（7）与4-肼基-酞嗪酮的反应产生3,5-双-芳基-N-杂芳基-吡唑啉（8）或相应的烯-（9）。新化合物的结构由IR [ 1]建立。H和13 C NMR光谱，包括DNOE，HMQC，HMBC和DEPT方法。对于化合物1b，3b和8b，还通过X射线衍射阐明了立体结构。
• Novel ring transformations of condensed [1,2,4]triazolo[4,3-b]pyridazine-6(5H)-one-3(2H)-thiones effected by dialkyl-acetylenedicarboxylates
  作者：Mónika Simó、Antal Csámpai、Veronika Harmat、Orsolya Barabás、Gábor Magyarfalvy

  DOI：10.1016/s0040-4020(01)00672-x

  日期：2001.8

  On heating with dialkyl-acetylenedicarboxylates in DMF condensed [1,2,4]-triazolo[4,3-b] pyridazine-6(5H)-one-3(2H)-thiones undergo unprecedented ring transformations yielding novel tetracyclic 1,3-diazepines and thiazolotriazole derivatives depending on the applied reaction temperature. The observed substrate selectivity was interpreted on the basis of the results of comparative theoretical calculations carried out at semiempirical level (AMI). (C) 2001 Elsevier Science Ltd. All rights reserved.
• Schneider; Siegmund; Zschmiesche, Pharmazie, 1988, vol. 43, # 1, p. 33 - 36
  作者：Schneider、Siegmund、Zschmiesche、Kallwellis、Scherber

  DOI：——

  日期：——