1-phenyl-2H,4H-tetrahydro-1,2,4-triazin-3-thione | 122610-88-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 1-phenyl-2H,4H-tetrahydro-1,2,4-triazin-3-thione
• 英文别名: 1,2,4-Triazine-3(2H)-thione, tetrahydro-1-phenyl-；1-phenyl-1,2,4-triazinane-3-thione
• CAS: 122610-88-2
• 化学式: C₉H₁₁N₃S
• 分子量: 193.272
• InChiKey: ZKISIFZRLGMBKW-UHFFFAOYSA-N

物化性质

• 沸点：
  293.1±23.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  59.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-(2-(苯基氨基)乙基)氨基甲酸乙酯 在 劳森试剂 、 盐酸 、 乙基溴化镁 、 溶剂黄146 、 锌 、 sodium nitrite 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 66.5h， 生成 1-phenyl-2H,4H-tetrahydro-1,2,4-triazin-3-thione
  参考文献：
  名称：

  5-Lipoxygenase Inhibitors:  Synthesis and Structure−Activity Relationships of a Series of 1-Aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones

  摘要：

  Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human blood assays with IC50 values of 5-21 mu M. In a rat anaphylaxis model, 4 blocked leukotriene formation with an ED(50) = 7 mg/kg when administered orally. Compound 4 exhibited selectivity for inhibition of 5-LO with little activity against related enzymes: 12-LO from human platelets, 15-LO from soybean, and cyclooxygenase (COX) from sheep seminal vesicle. In pilot subacute toxicity testing, 4 did not produce methemoglobinemia in rats (400 mg/kg po daily for 9 days) or in dogs (200 mg/kg po daily for 28 days). These results indicated that the triazinone structure provided a 5-LO inhibitor template devoid of the toxicity problems observed in the related phenidone (1) and pyridazinone (3) classes of 5-LO inhibitors. The parent compound 4 is a selective, orally bioavailable 5-LO inhibitor which can serve as a useful reference standard for in vivo pharmacological studies involving leukotriene-mediated phenonmena.

  DOI：

  10.1021/jm960372b

文献信息

• New Advances in the Synthesis of Emerging Cyclic Amidrazones to Foster Bioisosterism of Azaheterocycles
  作者：Johann Leblanc、Monique Mathé‐Allainmat、Sandrine Grosse、Jérôme Guillemont、Arnaud Tessier、Jacques Lebreton

  DOI：10.1002/ejoc.202300033

  日期：2023.3.7

  constitute essential molecular units that are found in natural products, in medicinal chemistry, in materials, catalysis, and so on. This work discloses a robust method to access original cyclic amidrazones as new scaffold within an uncharted chemical space.

  氮杂杂环在自然界和合成化学中无处不在，构成了天然产物、药物化学、材料、催化等中的基本分子单元。这项工作公开了一种稳健的方法，可以在未知的化学空间中获取原始环状氨基腙作为新支架。
• Pyridazinone, triazinone and oxapyridazinone lipoxygenase inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0299449A2

  公开（公告）日：1989-01-18

  Pyridazinone, triazinone and oxapyridazinone compounds which are useful in inhibting lipoxygenase enzymes, particularly 5-lipoxygenase.

  可抑制脂氧合酶，特别是 5-脂氧合酶的哒嗪酮、三嗪酮和噁哒嗪酮化合物。
• US4970210A
  申请人：——

  公开号：US4970210A

  公开（公告）日：1990-11-13
• US5086052A
  申请人：——

  公开号：US5086052A

  公开（公告）日：1992-02-04
• 5-Lipoxygenase Inhibitors:  Synthesis and Structure−Activity Relationships of a Series of 1-Aryl-2<i>H</i>,4<i>H</i>-tetrahydro-1,2,4-triazin-3-ones
  作者：Pramila A. Bhatia、Clint D. W. Brooks、Anwer Basha、James D. Ratajczyk、Bruce P. Gunn、Jennifer B. Bouska、Carmine Lanni、Patrick R. Young、Randy L. Bell、George W. Carter

  DOI：10.1021/jm960372b

  日期：1996.1.1

  Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human blood assays with IC50 values of 5-21 mu M. In a rat anaphylaxis model, 4 blocked leukotriene formation with an ED(50) = 7 mg/kg when administered orally. Compound 4 exhibited selectivity for inhibition of 5-LO with little activity against related enzymes: 12-LO from human platelets, 15-LO from soybean, and cyclooxygenase (COX) from sheep seminal vesicle. In pilot subacute toxicity testing, 4 did not produce methemoglobinemia in rats (400 mg/kg po daily for 9 days) or in dogs (200 mg/kg po daily for 28 days). These results indicated that the triazinone structure provided a 5-LO inhibitor template devoid of the toxicity problems observed in the related phenidone (1) and pyridazinone (3) classes of 5-LO inhibitors. The parent compound 4 is a selective, orally bioavailable 5-LO inhibitor which can serve as a useful reference standard for in vivo pharmacological studies involving leukotriene-mediated phenonmena.