2-[[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino]benzoic acid

• 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: 2-[[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino]benzoic acid
• 英文别名: 2-{[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino}benzoic acid；2-[(4,6-dioxo-2-thioxo-tetrahydropyrimidin-5(6H)ylidene)methylamino]benzoic acid；2-[(4,6-dioxo-2-sulfanylidene-1,3-diazinan-5-ylidene)methylamino]benzoic acid
• 化学式: C₁₂H₉N₃O₄S
• 分子量: 291.287
• InChiKey: UNMBLQZTAKRNCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.21
• 重原子数：
  20.0
• 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：
  107.53
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  邻氨基苯甲酸 、 5-dimethylaminomethylene-2-thiobarbituric acid 以 乙醇 为溶剂， 以96%的产率得到2-[[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]amino]benzoic acid
  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

• Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies
  作者：Abdul Rauf、Sohail Shahzad、Marek Bajda、Muhammad Yar、Faiz Ahmed、Nazar Hussain、Muhammad Nadeem Akhtar、Ajmal Khan、Jakub Jończyk

  DOI：10.1016/j.bmc.2015.05.038

  日期：2015.9

  In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1–9 and 19–27) were found to exhibit low to moderate activity however thiobarbituric

  在这项研究中，在原甲酸三乙酯存在下，通过缩合巴比妥酸或硫代巴比妥酸和各自的苯胺（带有不同的取代基），合成了36种新化合物。对波克豆脲酶的体外脲酶抑制研究表明，发现巴比妥酸衍生的化合物（1 – 9和19 – 27）显示出低至中等的活性，而硫代巴比妥酸衍生的化合物（10 – 18和28 – 36）显示出显着的抑制活性。在低摩尔浓度下。在合成的化合物中，化合物（15），（12），（10），（36），（16）和（35）表现出出色的脲酶抑制作用，IC 50值分别为8.53±0.027、8.93±0.027、12.96±0.13、15±0.098、18.9±0.027和19.7±0.63μM优于参考化合物硫脲（IC 50  = 21±0.011）。化合物（11）表现出与标准品相当的活性，IC 50值为21.83±0.19μM。在计算机上对大多数活性化合物（10），（12），（15），（16），（35）
• Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents
  作者：Joana Figueiredo、João L. Serrano、Eunice Cavalheiro、Leena Keurulainen、Jari Yli-Kauhaluoma、Vânia M. Moreira、Susana Ferreira、Fernanda C. Domingues、Samuel Silvestre、Paulo Almeida

  DOI：10.1016/j.ejmech.2017.11.070

  日期：2018.1

  acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro.

  由于其广泛的生物活性，巴比妥酸和硫代巴比妥酸衍生物已逐渐对药物化学家产生吸引力。本文中，以中等至优异的产率制备了不同系列的1,3,5-三取代的巴比妥酸酯和硫代巴比妥酸酯，并在体外评估了它们作为黄嘌呤氧化酶抑制剂，抗氧化剂，抗菌剂和抗增殖化合物的活性。发现有趣的生物活性巴比妥酸酯，即1,3-二甲基-5- [1-（2-（苯基肼基）亚乙基]嘧啶-2,4,6（1 H，3 H，5 H）-三酮（6c）和1， 3-二甲基-5- [1- [2-（4-硝基苯基）肼基]亚乙基]嘧啶-2,4,6（1 H，3 H，5H）-三酮（6e），其显示出同时发生的黄嘌呤氧化酶抑制作用（IC 50值分别为24.3和27.9μM）和2,2-二苯基-1-吡啶并肼基（DPPH）自由基清除活性（IC 50值为18.8）和23.8μM）。此外，5- [1-（2-苯基肼基）亚乙基]嘧啶-2,4,6（1 H，3 H，5 H）-三酮（6d）
• 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.