2-[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]-N-phenylhydrazine carbothioamide | 1491159-60-4

• 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: 2-[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]-N-phenylhydrazine carbothioamide
• 英文别名: 1-[(tetrahydro-4,6-dioxo-2-thioxopyrimidin-5(6H)-ylidene)methyl]-4-phenylthiosemicarbazide；1-[(4,6-dioxo-2-sulfanylidene-1,3-diazinan-5-ylidene)methylamino]-3-phenylthiourea
• CAS: 1491159-60-4
• 化学式: C₁₂H₁₁N₅O₂S₂
• 分子量: 321.384
• InChiKey: WLNANLBGOPNLGX-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C (decomp)
• 密度：
  1.56±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.11
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  94.29
• 氢给体数：
  5.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  5-dimethylaminomethylene-2-thiobarbituric acid 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]-N-phenylhydrazine carbothioamide
  参考文献：
  名称：

  New thiobarbituric acid scaffold-based small molecules: Synthesis, cytotoxicity, 2D-QSAR, pharmacophore modelling and in-silico ADME screening

  摘要：

  A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4-7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Compound 12d exhibited potent sub-micromolar activity against HepG-2 and MCF-7 (IC50 = 0.07 and 0.08 mu M, respectively). In-silico pharmacophore modelling of this chemotype compounds disclosed a five features' pharmacophore model representing essential steric and electronic fingerprints essential for activity. Finally, a 2D-QSAR model was devised to quantitatively correlate the 2D molecular feature descriptors of this series of thiobarbiturates with their cytotoxic activity against MCF-7. Finally, in silico evaluation of the physicochemical and ADME properties of these derivatives was performed.

  DOI：

  10.1016/j.ejps.2019.01.023

文献信息

• Synthesis, molecular docking studies, and in vitro screening of barbiturates/thiobarbiturates as antibacterial and cholinesterase inhibitors
  作者：Saira Mumtaz、Rashad Hussain、Abdul Rauf、M. Q. Fatmi、H. Bokhari、M. Oelgemöller、A. M. Qureshi

  DOI：10.1007/s00044-013-0847-2

  日期：2014.6

  On the basis of observed biological activity of barbiturates/thiobarbiturates, a set of 13 hydrazinecarboxamide/hydrazinecarbothioamides derivatives were designed and synthesized in good to excellent yield with extensive structural characterization. These compounds were screened for antibacterial and cholinesterase inhibitory activities. Two of the compounds 1 and 2 showed moderate bactericidal activity. Compounds 10 and 4 were found to be the most active acetyl/butyryl cholinesterase inhibitor, respectively (AChEI; 10; IC50 = 40.78 mu M and BChEI; 4; IC50 = 3.31 mu M). In silico molecular docking studies were carried out to identify active interacting sites of drug and enzyme and to establish structure-activity relationships. When predicted cholinesterase binding energies were compared with the experimentally determined inhibitory concentrations (IC50), most active compounds were also found to be the most favorable for binding. The binding scores of compounds 10 and 4 were -10.2 and -9.3 kcal/mol, respectively.
• New thiobarbituric acid scaffold-based small molecules: Synthesis, cytotoxicity, 2D-QSAR, pharmacophore modelling and in-silico ADME screening
  作者：Heba S.A. El-Zahabi、Maha M.A. Khalifa、Yomna M.H. Gado、Amel M. Farrag、Mahmoud M. Elaasser、Nesreen A. Safwat、Reham R. AbdelRaouf、Reem K. Arafa

  DOI：10.1016/j.ejps.2019.01.023

  日期：2019.3

  A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4-7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Compound 12d exhibited potent sub-micromolar activity against HepG-2 and MCF-7 (IC50 = 0.07 and 0.08 mu M, respectively). In-silico pharmacophore modelling of this chemotype compounds disclosed a five features' pharmacophore model representing essential steric and electronic fingerprints essential for activity. Finally, a 2D-QSAR model was devised to quantitatively correlate the 2D molecular feature descriptors of this series of thiobarbiturates with their cytotoxic activity against MCF-7. Finally, in silico evaluation of the physicochemical and ADME properties of these derivatives was performed.