4-(4-chlorophenyl)-1-(4-fluorobenzoyl)-thiosemicarbazide | 54543-18-9

• 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: 4-(4-chlorophenyl)-1-(4-fluorobenzoyl)-thiosemicarbazide
• 英文别名: 1-(4-Fluorbenzoyl)-4-(4-chlorphenyl)-thiosemicarbazid；1-(4-Chlorophenyl)-3-[(4-fluorobenzoyl)amino]thiourea
• CAS: 54543-18-9
• 化学式: C₁₄H₁₁ClFN₃OS
• 分子量: 323.778
• InChiKey: JJNVSXJYSOJWGI-UHFFFAOYSA-N

物化性质

• 密度：
  1.448±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-chlorophenyl)-1-(4-fluorobenzoyl)-thiosemicarbazide 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 2.0h， 生成 4-(4-chlorophenyl)-5-(4-fluorophenyl)-2,4-dihydro-1,2,4-triazole-3-thione
  参考文献：
  名称：

  Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

  摘要：

  耐药性细菌的产生是目前医学界面临的主要挑战之一。因此，迫切需要发现新的先导结构来设计抗菌药物。在这项结构-活性关系研究中，我们建立了一个由正氟、偏氟和对氟苯甲酰基硫代氨基脲及其 1,2,4-三唑支架环状类似物组成的化合物库，并测试了它们对革兰氏阳性菌株的抗菌活性。虽然所有测试的 1,2,4-三唑类化合物都不具有强效活性，但硫代氨基甲酸盐的抗菌反应与 N4 芳基位置的取代模式有很大关系。15a、15b 和 16b 等三氟甲基衍生物的活性最佳，它们对参考菌株、对甲氧西林敏感的致病性金黄色葡萄球菌和对甲氧西林耐药的金黄色葡萄球菌临床分离株都有活性，最小抑菌浓度 (MIC) 为 7.82 至 31.25 μg/mL。根据对接得到的结合亲和力，可以得出结论，氟苯甲酰基硫代氨基甲酸盐可被视为潜在的异位d-丙氨酰-d-丙氨酸连接酶抑制剂。

  DOI：

  10.3390/molecules26010170
• 作为产物：
  描述：

  4-氟苯甲酸苯酯 在 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.5h， 生成 4-(4-chlorophenyl)-1-(4-fluorobenzoyl)-thiosemicarbazide
  参考文献：
  名称：

  1,3,4-Thiadiazole Derivatives. Synthesis, Structure Elucidation, and Structure−Antituberculosis Activity Relationship Investigation

  摘要：

  A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized, the compounds structures were elucidated and screened for the antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the tested compounds, 2-phenylamino-5-(4-fluorophenyl)-1,3,4-thiadiazole 22 showed the highest inhibitory activity. The relationships between the structures of compounds and their antituberculosis activity were investigated by the Electronic-Topological Method (ETM) and feed forward neural networks (FFNNs) trained with the back-propagation algorithm. As a result of the approach, a system of pharmacophores and anti-pharmacophores has been found that effectively separates compounds of the examination set into groups of active and inactive compounds. The system can be applied to the screening and design of new active compounds possessing skeletons similar to those used in the present study.

  DOI：

  10.1021/jm0495632

文献信息

• Preparation and antiarthritic activity of new 1,5-diaryl-3-alkylthio-1H-1,2,4-triazoles and corresponding sulfoxides and sulfones
  作者：G SZILAGYI

  DOI：10.1016/0223-5234(90)90015-u

  日期：1990.3
• Discovery of Protein–Protein Interaction Inhibitors of Replication Protein A
  作者：James D. Patrone、J. Phillip Kennedy、Andreas O. Frank、Michael D. Feldkamp、Bhavatarini Vangamudi、Nicholas F. Pelz、Olivia W. Rossanese、Alex G. Waterson、Walter J. Chazin、Stephen W. Fesik

  DOI：10.1021/ml400032y

  日期：2013.7.11

  Replication protein A (RPA) is a ssDNA binding protein that is essential for DNA replication and repair. The initiation of the DNA damage response by RPA is mediated by protein protein interactions involving the N-terminal domain of the 70 kDa subunit with partner proteins. Inhibition of these interactions increases sensitivity toward DNA damage and replication stress and may therefore be a potential strategy for cancer drug discovery. Toward this end, we have discovered two lead series of compounds, derived from hits obtained from a fragment-based screen that bind to RPA70N with low micromolar affinity and inhibit the binding of an ATRIP-derived peptide to RPA. These compounds may offer a promising starting point for the discovery of clinically useful RP inhibitors.
• 1,3,4-Thiadiazole Derivatives. Synthesis, Structure Elucidation, and Structure−Antituberculosis Activity Relationship Investigation
  作者：Elçin E. Oruç、Sevim Rollas、Fatma Kandemirli、Nathaly Shvets、Anatholy S. Dimoglo

  DOI：10.1021/jm0495632

  日期：2004.12.1

  A series of 2,5-disubstituted-1,3,4-thiadiazoles were synthesized, the compounds structures were elucidated and screened for the antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the tested compounds, 2-phenylamino-5-(4-fluorophenyl)-1,3,4-thiadiazole 22 showed the highest inhibitory activity. The relationships between the structures of compounds and their antituberculosis activity were investigated by the Electronic-Topological Method (ETM) and feed forward neural networks (FFNNs) trained with the back-propagation algorithm. As a result of the approach, a system of pharmacophores and anti-pharmacophores has been found that effectively separates compounds of the examination set into groups of active and inactive compounds. The system can be applied to the screening and design of new active compounds possessing skeletons similar to those used in the present study.
• Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold
  作者：Urszula Kosikowska、Monika Wujec、Nazar Trotsko、Wojciech Płonka、Piotr Paneth、Agata Paneth

  DOI：10.3390/molecules26010170

  日期：——

  The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

  耐药性细菌的产生是目前医学界面临的主要挑战之一。因此，迫切需要发现新的先导结构来设计抗菌药物。在这项结构-活性关系研究中，我们建立了一个由正氟、偏氟和对氟苯甲酰基硫代氨基脲及其 1,2,4-三唑支架环状类似物组成的化合物库，并测试了它们对革兰氏阳性菌株的抗菌活性。虽然所有测试的 1,2,4-三唑类化合物都不具有强效活性，但硫代氨基甲酸盐的抗菌反应与 N4 芳基位置的取代模式有很大关系。15a、15b 和 16b 等三氟甲基衍生物的活性最佳，它们对参考菌株、对甲氧西林敏感的致病性金黄色葡萄球菌和对甲氧西林耐药的金黄色葡萄球菌临床分离株都有活性，最小抑菌浓度 (MIC) 为 7.82 至 31.25 μg/mL。根据对接得到的结合亲和力，可以得出结论，氟苯甲酰基硫代氨基甲酸盐可被视为潜在的异位d-丙氨酰-d-丙氨酸连接酶抑制剂。