3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one | 102353-65-1

• 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: 3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one
• 英文别名: 3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-one；3-methyl-5H-[1,2,4]triazolo[3,4-a]phthalazin-6-one
• CAS: 102353-65-1
• 化学式: C₁₀H₈N₄O
• 分子量: 200.2
• InChiKey: GTGVPBYAENFIOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one 在 乙酸酐 、 一水合肼 作用下， 反应 1.0h， 生成 3-(6-oxo-5H-[1,2,4]triazolo[3,4-a]phthalazin-3-yl)-5-phenyl-3,4-dihydropyrazole-2-carbaldehyde
  参考文献：
  名称：

  一些具有抗炎和抗菌活性的三唑并酞嗪衍生物的合成

  摘要：

  几个新系列的三唑并酞嗪衍生物，即；吡唑基乙烯基三唑并酞嗪酮 (4a – d)、苯乙烯基三唑并酞嗪酮 (5a, b)、芳基氧代丙烯基三唑并酞嗪酮 (7a, b)、吡唑啉基- (8a, b)、(9a, b) 和 (10a – f)、吡唑基-(11恶唑) -5-yl) -1,2,4-triazolo [3,4-a] phthalazin-6 (5H) -ones (14a, b), triazolo [3,4-a] phthalazin-3 -Yl-pyridine- 3-腈（12a，b），三唑并[3，4-a]酞嗪-3-基）乙基硫代乙酸（13a，b）和2-芳基-5-芳基氨基-1H，5H-吡唑并[2”，3” -1 ', 5 '] 咪唑并 [3 ', 4'-1,5] -1,2,4-triazolo [3,4-a] phthalazin-12 (13H) -ones (15a–c) 已合成. 已经研究了代表性化合物的抗炎活性。化合物

  DOI：

  10.1002/ardp.201100053
• 作为产物：
  描述：

  1,4-二氯酞嗪 在 一水合肼 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one
  参考文献：
  名称：

  发现作为 DNA 嵌入剂和拓扑异构酶 II 抑制剂的新型三唑并酞嗪衍生物

  摘要：

  设计并合成了一系列新的三唑并酞嗪衍生物作为拓扑异构酶 II (Topo II) 抑制剂和 DNA 嵌入剂。在体外评估了合成的衍生物对三种人类癌细胞系的细胞毒活性：HepG2、MCF-7 和 HCT-116 细胞。化合物IX b是最有效的对应物，IC 50值为 5.39 ± 0.4、3.81 ± 0.2 和 4.38 ± 0.3 µM，因为它的活性大约是阿霉素的 1.47、1.77 和 1.19 倍（IC 50  = 7.6,4 ± 6.75 ± 0.4 和 5.23 ± 0.3 µM）分别针对 HepG2、MCF-7 和 HCT-116 细胞。此外，合成化合物对 DNA 分子的结合亲和力使用 DNA/甲基绿测定进行评估。化合物 Ⅸ b显示出优异的 DNA 结合亲和力，IC 50值为 27.16 ± 1.2 µM，优于参考药物阿霉素 (IC 50  = 31.02 ± 1.80 µM)。此外，当研究它们的

  DOI：

  10.1002/ardp.202000456

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。
• 3-Phenyl-6-(2-pyridyl)methyloxy-1,2,4-triazolo[3,4-<i>a</i>]phthalazines and Analogues:  High-Affinity γ-Aminobutyric Acid-A Benzodiazepine Receptor Ligands with α2, α3, and α5-Subtype Binding Selectivity over α1
  作者：Robert W. Carling、Kevin W. Moore、Leslie J. Street、Deborah Wild、Catherine Isted、Paul D. Leeson、Steven Thomas、Desmond O'Connor、Ruth M. McKernan、Katherine Quirk、Susan M. Cook、John R. Atack、Keith A. Wafford、Sally A. Thompson、Gerard R. Dawson、Pushpinder Ferris、José L. Castro

  DOI：10.1021/jm031020p

  日期：2004.3.1

  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.