1-(3-chlorobenzoyl)-4-isobutylthiosemicarbazide | 26036-06-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(3-chlorobenzoyl)-4-isobutylthiosemicarbazide
• 英文别名: 1-[(3-Chlorobenzoyl)amino]-3-(2-methylpropyl)thiourea；1-[(3-chlorobenzoyl)amino]-3-(2-methylpropyl)thiourea
• CAS: 26036-06-6
• 化学式: C₁₂H₁₆ClN₃OS
• 分子量: 285.798
• InChiKey: SJJZIXLQUSQNFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-chlorobenzoyl)-4-isobutylthiosemicarbazide 在 硫酸 作用下， 生成 [5-(3-chloro-phenyl)-[1,3,4]thiadiazol-2-yl]-isobutyl-amine
  参考文献：
  名称：

  3-芳基（或吡啶基）-5-烷基（或芳基）氨基-1,3,4-噻二唑和4H-1,2,4-三唑的一些磺酰脲衍生物的合成及降血糖活性。

  摘要：

  DOI：

  10.1021/jm00292a035
• 作为产物：
  描述：

  异硫氰酸异丁酯 、 3-氯苯甲酰肼 反应 0.08h， 以82%的产率得到1-(3-chlorobenzoyl)-4-isobutylthiosemicarbazide
  参考文献：
  名称：

  Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies

  摘要：

  The treatment of epilepsy remains difficult mostly since almost 30% of patients suffer from pharmacoresistant forms of the disease. Therefore, there is an urgent need to search for new antiepileptic drug candidates. Previously, it has been shown that 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivativatives possessed strong anticonvulsant activity in a maximal electroshock-induced seizure model of epilepsy. In this work, we examined the effect of the chemical structure of the 1,2,4-triazole-3-thione-based molecules on the anticonvulsant activity and the binding to voltage-gated sodium channels (VGSCs) and GABA(A) receptors. Docking simulations allowed us to determine the mode of interactions between the investigated compounds and binding cavity of the human VGSC. Selected compounds were also investigated in a panel of ADME-Tox assays, including parallel artificial membrane permeability assay (PAMPA), single cell gel electrophoresis (SCGE) and cytotoxicity evaluation in HepG2 cells. The obtained results indicated that unbranched alkyl chains, from butyl to hexyl, attached to 1,2,4-triazole core are essential both for good anticonvulsant activity and strong interactions with VGSCs. The combined in-vivo, in-vitro and in-silico studies emphasize 4-alkyl-5-substituted-1,2,4-triazole-3-thiones as promising agents in the development of new anticonvulsants.

  DOI：

  10.1016/j.ejps.2018.12.018

文献信息

• Synthesis and hypoglycemic activity of 3-aryl(or pyridyl)-5-alkyl(or aryl)amino-1,3,4-thiadiazoles and some sulfonylurea derivatives of 4H-1,2,4-triazoles
  作者：C. V. Deliwala、M. Y. Mhasalkar、M. H. Shah、P. D. Pilankar、S. T. Nikam、K. G. Anantanarayanan

  DOI：10.1021/jm00292a035

  日期：1971.10
• Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies
  作者：Barbara Kaproń、Jarogniew J. Łuszczki、Anita Płazińska、Agata Siwek、Tadeusz Karcz、Anna Gryboś、Gabriel Nowak、Anna Makuch-Kocka、Katarzyna Walczak、Ewa Langner、Karolina Szalast、Sebastian Marciniak、Magdalena Paczkowska、Judyta Cielecka-Piontek、Lukasz M. Ciesla、Tomasz Plech

  DOI：10.1016/j.ejps.2018.12.018

  日期：2019.3

  The treatment of epilepsy remains difficult mostly since almost 30% of patients suffer from pharmacoresistant forms of the disease. Therefore, there is an urgent need to search for new antiepileptic drug candidates. Previously, it has been shown that 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivativatives possessed strong anticonvulsant activity in a maximal electroshock-induced seizure model of epilepsy. In this work, we examined the effect of the chemical structure of the 1,2,4-triazole-3-thione-based molecules on the anticonvulsant activity and the binding to voltage-gated sodium channels (VGSCs) and GABA(A) receptors. Docking simulations allowed us to determine the mode of interactions between the investigated compounds and binding cavity of the human VGSC. Selected compounds were also investigated in a panel of ADME-Tox assays, including parallel artificial membrane permeability assay (PAMPA), single cell gel electrophoresis (SCGE) and cytotoxicity evaluation in HepG2 cells. The obtained results indicated that unbranched alkyl chains, from butyl to hexyl, attached to 1,2,4-triazole core are essential both for good anticonvulsant activity and strong interactions with VGSCs. The combined in-vivo, in-vitro and in-silico studies emphasize 4-alkyl-5-substituted-1,2,4-triazole-3-thiones as promising agents in the development of new anticonvulsants.