3-(3-methylphenyl)-2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thione | 1450820-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并哒嗪类
• 英文名称: 3-(3-methylphenyl)-2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thione
• 英文别名: 1-(3-Methylphenyl)-1,2,5,6,7,8-hexahydro-[1,2,4]triazolo[1,2-a]pyridazine-3-thione；1-(3-methylphenyl)-1,2,5,6,7,8-hexahydro-[1,2,4]triazolo[1,2-a]pyridazine-3-thione
• CAS: 1450820-02-6
• 化学式: C₁₃H₁₇N₃S
• 分子量: 247.364
• InChiKey: JWAHMUUEBIDOFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  50.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-methylphenyl)-2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thione 、 碘甲烷 以 二氯甲烷 为溶剂， 反应 84.0h， 以38%的产率得到methyl[3-(3-methylphenyl)-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-1-ylidene]sulfonium iodide
  参考文献：
  名称：

  1-取代的3-甲基硫烷基-5,6,7,8-四氢-1H- [1,2,4]三唑并[1,2-a]哒嗪的合成，化学行为，结构解析和iNOS抑制活性。

  摘要：

  新型纤细且形状丰富的富含sp3的氮杂环系统是在铅发现中扩展分子多样性的广受欢迎的平台。本工作描述了迄今为止未知的3-甲基硫基-5,6,7,8-四氢-1H- [1,2,4]三唑并[1,2-a]哒嗪2的一系列衍生物的合成和表征。此方法由一项计算研究指导，旨在优化先前报道的已知抑制诱导型一氧化氮合酶（iNOS）的[1,2,4]三唑并[1,2-a]哒嗪-1-硫酮1。在温和条件下通过化合物1的甲基化可得到标题化合物。使用RINm5F细胞，通过与应用于1型先前产品相同的基于细胞的分析，对产品进行了生物学评估，在促炎细胞因子IL-1β和IFN-γ的作用下刺激它们产生NO。化合物2在所选测定中未显示出预期的iNOS抑制活性的改善，但有助于该领域的SAR。另外，已经研究了通过氧化前所未有地形成副产物3。新颖的支架代表了构建各种分子的有吸引力的起点，这些分子与基于扁平和亲脂性芳族支架的已知化合物有很大不同。

  DOI：

  10.1691/ph.2017.6902
• 作为产物：
  描述：

  四氢-1(2H)-哒嗪硫代甲酰胺 、 3-甲基苯甲醛 在 对甲苯磺酸 作用下， 以 水 为溶剂， 反应 0.42h， 以68%的产率得到3-(3-methylphenyl)-2,3,5,6,7,8-hexahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1-thione
  参考文献：
  名称：

  Investigations on synthesis and structure elucidation of novel [1,2,4]triazolo[1,2-a]pyridazine-1-thiones and their inhibitory activity against inducible nitric oxide synthase

  摘要：

  The inducible nitric oxide synthase (iNOS) is a target of great research interest due to its importance in a number of diseases, for example, septic shock and inflammatory lung diseases. A variety of 3-substituted [1,2,4]triazolo[1,2-a]pyridazine derivatives was synthesized by ring closure with hexahydropyridazinel-1-carbothioamide by using aliphatic and aromatic aldehydes. The activity of the new substances was tested on the insulin-secreting rat insulinoma cell line RINm5F. iNOS was expressed through exposure to interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). A number of the investigated compounds were more active than the reference inhibitor aminoguanidine (AG). Structure-activity relationships showed that a phenyl substituent in position 3 is apparently essential for inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.064

文献信息

• Investigations on synthesis and structure elucidation of novel [1,2,4]triazolo[1,2-a]pyridazine-1-thiones and their inhibitory activity against inducible nitric oxide synthase
  作者：Ulrike Schulz、Antje Grossmann、Manja Witetschek、Christian Lemmerhirt、Marcus Polzin、Beate Haertel、Heike Wanka、Olaf Morgenstern

  DOI：10.1016/j.bmc.2013.05.064

  日期：2013.9

  The inducible nitric oxide synthase (iNOS) is a target of great research interest due to its importance in a number of diseases, for example, septic shock and inflammatory lung diseases. A variety of 3-substituted [1,2,4]triazolo[1,2-a]pyridazine derivatives was synthesized by ring closure with hexahydropyridazinel-1-carbothioamide by using aliphatic and aromatic aldehydes. The activity of the new substances was tested on the insulin-secreting rat insulinoma cell line RINm5F. iNOS was expressed through exposure to interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). A number of the investigated compounds were more active than the reference inhibitor aminoguanidine (AG). Structure-activity relationships showed that a phenyl substituent in position 3 is apparently essential for inhibition. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis, chemical behavior, structure elucidation and iNOS inhibitory activity of 1-substituted 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines+
  作者：Schulz、Grossmann、Wilde、Freitag、Lemmerhirt、Schulzke、Link、Morgenstern

  DOI：10.1691/ph.2017.6902

  日期：——

  Novel slim and shapely sp3-rich nitrogen containing heterocyclic ring systems are sought-after platforms for the expansion of molecular diversity in lead discovery. The present work describes the synthesis and characterization of a series of derivatives of hitherto unknown 3-methylsulfanyl-5,6,7,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazines 2. This approach was guided by a computational study,

  新型纤细且形状丰富的富含sp3的氮杂环系统是在铅发现中扩展分子多样性的广受欢迎的平台。本工作描述了迄今为止未知的3-甲基硫基-5,6,7,8-四氢-1H- [1,2,4]三唑并[1,2-a]哒嗪2的一系列衍生物的合成和表征。此方法由一项计算研究指导，旨在优化先前报道的已知抑制诱导型一氧化氮合酶（iNOS）的[1,2,4]三唑并[1,2-a]哒嗪-1-硫酮1。在温和条件下通过化合物1的甲基化可得到标题化合物。使用RINm5F细胞，通过与应用于1型先前产品相同的基于细胞的分析，对产品进行了生物学评估，在促炎细胞因子IL-1β和IFN-γ的作用下刺激它们产生NO。化合物2在所选测定中未显示出预期的iNOS抑制活性的改善，但有助于该领域的SAR。另外，已经研究了通过氧化前所未有地形成副产物3。新颖的支架代表了构建各种分子的有吸引力的起点，这些分子与基于扁平和亲脂性芳族支架的已知化合物有很大不同。