4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiol | 219600-07-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiol
• 英文别名: 4-methyl-3-pyrazin-2-yl-1H-1,2,4-triazole-5-thione
• CAS: 219600-07-4
• 化学式: C₇H₇N₅S
• mdl: MFCD07364219
• 分子量: 193.232
• InChiKey: BBRYQLIJAGCOHU-UHFFFAOYSA-N

物化性质

• 沸点：
  303.0±45.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

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：
  0.142
• 拓扑面积：
  85.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiol 在 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 2-{4-methyl-5-[(3-{1-[4-(trifluoromethyl)phenyl]octahydropyrrolo[2,3-b]pyrrol-5-yl}propyl)sulfanyl]-4H-1,2,4-triazol-3-yl}pyrazine hydrochloride
  参考文献：
  名称：

  1,2,4-三唑基八氢吡咯并[2,3- b ]吡咯：一系列新的有效和选择性的多巴胺D3受体拮抗剂

  摘要：

  本文报道了一系列新的1,2,4-三唑基八氢吡咯并[2,3- b ]吡咯在DA D3受体上表现出高亲和力和选择性。鉴定了在hERG通道上具有高选择性的化合物，并对其药代动力学特性进行了全面分析。选择了一些具有适当可显影性的衍生物，以进一步研究并沿着筛选级联进行。特别地，衍生物60a（DA D3 p K i  ＝ 8.4，DA D2 p K i  ＝ 6.0和hERG fp K i  ＝ 5.2）显示出平衡的分布，并且围绕该分子进行进一步的改进。

  DOI：

  10.1016/j.bmc.2016.02.031
• 作为产物：
  描述：

  吡嗪-2-甲酰肼 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 4-methyl-5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiol
  参考文献：
  名称：

  Tryptophan and thiosemicarbazide derivatives: design, synthesis, and biological evaluation as potential β-d-galactosidase and β-d-glucosidase inhibitors

  摘要：

  Glycosidases, including beta-d-galactosidase and beta-d-glucosidase, are involved in a range of metabolic disorders, such as cancer, viral or bacterial infections, and diabetes. Previously, we scanned the pharmacophoric space of these enzymes and had a self-consistent and predictive quantitative structure-activity relationship that was used to identify several beta-d-galactosidase and beta-d-glucosidase inhibitors via in silico search of structural databases. Guided by the preceding modeling efforts, synthesis of a series of tryptophan and thiosemicarbazide derivatives as beta-d-galactosidase and beta-d-glucosidase inhibitors that match the generated pharmacophores followed by in vitro bioassay was carried out. Synthesized compounds 3c (37 % inhibition at 100 A mu M) and 4d (49 % inhibition at 100 A mu M) exhibited the best inhibitory bioactivities against beta-d-galactosidase and beta-d-glucosidase, respectively. They can serve as a promising lead compounds for the development of potential glycosidase inhibitors.

  DOI：

  10.1007/s00044-014-1314-4

文献信息

• [EN] DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A BICYCLO MOIETY<br/>[FR] ANTAGONISTES DU RÉCEPTEUR D3 DE LA DOPAMINE AYANT UN FRAGMENT BICYCLO
  申请人：INDIVIOR UK LTD

  公开号：WO2017021920A1

  公开（公告）日：2017-02-09

  The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.

  该披露提供了具有化学式（I）的化合物，其中取代基如本文所定义。这些化合物可用于调节多巴胺D3受体，并用于治疗与之相关的疾病，如成瘾、药物依赖和精神疾病。
• 1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists
  作者：Fabrizio Micheli、Alessia Bacchi、Simone Braggio、Laura Castelletti、Palmina Cavallini、Paolo Cavanni、Susanna Cremonesi、Michele Dal Cin、Aldo Feriani、Sylvie Gehanne、Mahmud Kajbaf、Luciano Marchió、Selena Nola、Beatrice Oliosi、Annalisa Pellacani、Elisabetta Perdonà、Anna Sava、Teresa Semeraro、Luca Tarsi、Silvia Tomelleri、Andrea Wong、Filippo Visentini、Laura Zonzini、Christian Heidbreder

  DOI：10.1021/acs.jmedchem.6b00972

  日期：2016.9.22

  A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with

  描述了一个新的1,2,4-三唑基5-氮杂螺[2.4]庚烷系列，对多巴胺（DA）D3受体（D3R）具有高亲和力和选择性。这些化合物中的一些在hERG通道上也具有很高的选择性，并且在铅鉴定和早期铅优化阶段的体内和体外药代动力学特性方面进行了表征。选择了一些具有总体良好的可开发性特征的衍生物用于进一步的后期铅优化研究。
• [EN] DOPAMINE D3 RECEPTOR ANTAGONISTS COMPOUNDS<br/>[FR] COMPOSÉS ANTAGONISTES DES RÉCEPTEURS D3 À LA DOPAMINE
  申请人：INDIVIOR UK LTD

  公开号：WO2016067043A1

  公开（公告）日：2016-05-06

  The disclosure is directed to novel dopamine D3 receptor antagonists, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, including treating drug dependency and psychosis.

  该披露涉及新型多巴胺D3受体拮抗剂，其制备方法，用于这些方法的中间体，含有它们的药物组合物以及它们在治疗中的用途，包括治疗药物依赖和精神病的用途。
• DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A MORPHOLINE MOIETY
  申请人：Indivior UK Limited

  公开号：US20180297990A1

  公开（公告）日：2018-10-18

  The disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof: The disclosure also provides processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them, and their use as modulators of dopamine D 3 receptors, such as treating substance abuse or psychiatric diseases.

  该公开提供了式(I)的化合物或其药用盐：该公开还提供了它们的制备方法，用于这些方法的中间体，含有它们的药物组合物，以及它们作为多巴胺D3受体调节剂的用途，例如治疗物质滥用或精神疾病。
• In situ generation of functionalized 1,2,4-triazole-5-thiones containing pyridine or pyrazine moieties and their coordination to Hg^II
  作者：Elena Bermejo、Alfonso Castiñeiras、Isabel García-Santos、Raúl Rodríguez-Riobó

  DOI：10.1039/c6ce00338a

  日期：——

  -triazole-5-thione). The complexes were isolated as solids and were characterized by elemental analysis, mass spectrometry and IR, 1H NMR and 13C NMR spectroscopy. Recrystallization of the complexes from DMSO gave the compounds [Hg(MPytat)2]n (3a), [Hg(HMPytat)2Br2]·H2O (4a), [Hg(HEPytat)(μ2-NS-EPytat)Cl2}2Hg] (6a), [Hg(EPytat)2]n (6b), [Hg(MPztat)2]n (10a) and [Hg(EPztat)2]n (11a) (HEPytat = 4-ethyl-5-pyridin-2-yl-2

  2-氰基吡啶或2-氰基吡嗪与N-甲基硫代氨基脲反应得到（Z）-2-（氨基（吡啶-2-基）亚甲基）-N-甲基肼基碳硫酰胺（HPyAm4M）和（Z）-2-（氨基（吡嗪） -2-基）亚甲基）-N-甲基肼甲硫基酰胺（HPzAm4M）。在这些硫代半脲化合物的合成中，在甲醇中长时间回流加热，导致形成4-甲基-5-吡啶-2--2-基-2,4-二氢-[1,2,4]三唑-5-硫酮（HMPytat，1）和4-甲基-5-吡嗪-2-基-2,4-二氢-[1,2,4]三唑-5-硫酮（HMPztat，2）通过起始硫代半氨基甲酮的氧化环化。硫半脲酮与汞的反应（II的）盐，得到通式[汞柱（TAT）X]（新配合物3，4）和[汞柱（Htat）2 X 2 ]（5，7，9-11），以及[氢化3（HEPytat）2（ EPytat）2 Cl 4 ]·3H 2 O（6）和[Hg（EPytat）（HEPytat）I]·H 2 O（8）（Htat