4-(4-fluorophenyl)-1-(4-hydroxybenzoyl)thiosemicarbazide | 314767-23-2

• 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-fluorophenyl)-1-(4-hydroxybenzoyl)thiosemicarbazide
• 英文别名: N-(4-fluorophenyl)-2-(4-hydroxybenzoyl)hydrazinecarbothioamide；1-(4-fluorophenyl)-3-[(4-hydroxybenzoyl)amino]thiourea
• CAS: 314767-23-2
• 化学式: C₁₄H₁₂FN₃O₂S
• 分子量: 305.333
• InChiKey: ZNRZSCHTHNPAEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  106
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-fluorophenyl)-1-(4-hydroxybenzoyl)thiosemicarbazide 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 1-cyclopropyl-6-fluoro-7-[4-{[4-(4-fluorophenyl)-3-(4-hydroxyphenyl)-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]methyl}piperazin-1-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids

  摘要：

  A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.058
• 作为产物：
  描述：

  对羟基苯甲酸甲酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 23.0h， 生成 4-(4-fluorophenyl)-1-(4-hydroxybenzoyl)thiosemicarbazide
  参考文献：
  名称：

  一些新型对羟基苯甲酰肼衍生物的合成、抗高血压活性和 3D-QSAR 研究

  摘要：

  p-羟基苯甲酰肼 2 用芳香族/脂肪族醛处理，然后用二硫化碳环化得到化合物 4a-4n。同样，化合物2通过处理取代的异硫氰酸酯然后处理氯乙酸产生相应的化合物6a-6i。通过无创血压测量和有创血压测量方法测定所有测试化合物的抗高血压活性。测试化合物显示出显着的抗高血压活性。完整的化合物进行了 3D-QSAR 研究。通过PHASE程序进行3D-QSAR分析，获得了具有良好预测能力（r2 = 0.98，q2 = 0.74）的统计可靠模型。

  DOI：

  10.1002/ardp.201000008

文献信息

• Synthesis, Antihypertensive Activity, and 3D-QSAR Studies of Some New p-Hydroxybenzohydrazide Derivatives
  作者：Ritesh P. Bhole、Kishore P. Bhusari

  DOI：10.1002/ardp.201000008

  日期：2011.2

  p‐Hydroxybenzohydrazide 2 on treatment with aromatic/aliphatic aldehyde followed by cyclization with carbon disulphide afforded compounds 4a–4n. Also, compound 2 by treatment of substituted isothiocyanate followed by the treatment of chloroacetic acid yields the corresponding compounds 6a–6i. All the test compounds were assayed for antihypertensive activity by non‐invasive blood pressure measurement

  p-羟基苯甲酰肼 2 用芳香族/脂肪族醛处理，然后用二硫化碳环化得到化合物 4a-4n。同样，化合物2通过处理取代的异硫氰酸酯然后处理氯乙酸产生相应的化合物6a-6i。通过无创血压测量和有创血压测量方法测定所有测试化合物的抗高血压活性。测试化合物显示出显着的抗高血压活性。完整的化合物进行了 3D-QSAR 研究。通过PHASE程序进行3D-QSAR分析，获得了具有良好预测能力（r2 = 0.98，q2 = 0.74）的统计可靠模型。
• Synthesis and 3D-QSAR of p-Hydroxybenzohydrazide Derivatives With Antimicrobial Activity Against Multidrug-Resistant Staphylococcus aureus
  作者：Ritesh P. Bhole、Kishore P. Bhusari

  DOI：10.5012/jkcs.2010.54.01.077

  日期：2010.2.20

  40여년전에 보고된 이래 병원에서 유래한 메치실린-저항 Staphylococcus aureus (MRSA) 은 세계적으로 큰 문제가 되어왔다. 항균성의 가능성을 가지는 새로운 약품을 개발하기 위하여 N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i)와 N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide (5.a-5.i)~(10.a-10.i)을 적절한 합성방법을 사용하여 합성하였다. 이들 합성된 화합물들은 s. aureus 균주에 대해 생체외 조건에서 분석하였다. 시료 화합물과 표준 화합물에 대해 최소억제농도(MIC)를 결정하였다. 시험한 모든 화합물들은 2000 $\mu}g$/mL 투여량까지는 독성이 없었고, 사용한 균주에 대해 상당한 항균성을 보였다. 특히 6.f, 7.g, 9.f 와 10.f, 10 i 들이 가장 항균성이 컸다. 이것으로 미루어 파라-히드록시벤조히드라자이드 고리와 치환된 싸이아졸린 고리는 항균성에 필수적임을 알 수 있었다. 3D-QSAR 분석결과로 파라-히드록시벤조히드라자이드의 활성자리에 대한 결합방식을 알게되었다. Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, Various N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i) and N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide from (5.a-5.i) to (10.a-10.i) were synthesized using appropriate synthetic route. The entire test compounds (4.a-4.i) and from (5.a-5.i) to (10.a-10.i) were assayed in vitro against s. aureus strain. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial activity against the strains used, when tested in vitro. In general, p-hydroxybenzohydrazide ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds 6.f, 7.g, 9.f and 10.f, 10 i were found to be most potent. The test compounds were found nontoxic upto the dose level of 2000 $\mu}g$/mL. The intact compounds were then subjected for 3D-QSAR studies. 3D-QSAR study based on the principal of alignment of pharmacophoric features by Schrodinger PHASE module. The 3D-QSAR study allowed us to confirm the preferential binding mode of p-hydroxybenzohydrazide inside the active site.

  医院获得性耐甲氧西林金黄色葡萄球菌（MRSA）自 40 多年前被报道以来，一直是一个重大的全球性问题。为了开发具有潜在抗菌活性的新药，我们采用适当的合成方法合成了 N'-[(-3-取代-4-氧代-1,3-噻唑烷-2-亚基]-4-羟基苯甲酰肼（4a-4.i）和 N'-[-(3,4-二取代)-1,3-噻唑烷-2-亚基)]-4-羟基苯甲酰肼（5.a-5.i）-（10.a-10.i）。这些合成化合物在体外条件下对金黄色葡萄球菌菌株进行了检测。测定了样品化合物和标准化合物的最低抑菌浓度（MIC）。所有测试化合物在剂量达到 2000 $\mu}g$/mL 时均无毒性，并对所用菌株显示出显著的抗菌活性，其中 6.f、7.g、9.f 和 10.f、10 i 的抗菌活性最强。这表明对羟基苯甲酰肼环和取代的环唑啉环对抗菌活性至关重要。3D-QSAR 分析揭示了对羟基苯甲酰肼与活性位点的结合模式。 自 40 多年前首次报道以来，医院获得性耐甲氧西林金黄色葡萄球菌（MRSA）已成为一个日益严重的全球性问题。为了研究具有潜在抗菌活性的新药线索，我们采用适当的合成路线合成了从(5.a-5.i)到(10.a-10.i)的各种 N'-[(-3-取代-4-氧代-1,3-噻唑烷-2-亚基]-4-羟基苯甲酰肼(4a-4.i)和 N'-[-(3,4-二取代)-1,3-噻唑烷-2-亚基)]-4-羟基苯甲酰肼。整个试验化合物（4.a-4.i）和（5.a-5.i）至（10.a-10.i）对金黄色葡萄球菌菌株进行了体外检测。测定了测试化合物和参考标准的最低抑菌浓度（MIC）。 在体外测试中，测试化合物对所用菌株具有显著的抗菌活性。 一般来说，对羟基苯甲酰肼环和取代的噻唑啉环对抗菌活性至关重要。 在测试的化合物中，化合物 6.f、7.g、9.f 和 10.f、10.i 的效力最强。测试化合物在 2000 $\mu}g$/mL 的剂量水平内均无毒性。 完整化合物随后进行了 3D-QSAR 研究。 3D-QSAR 研究基于 Schrodinger PHASE 模块的药效学特征排列原理。 3D-QSAR 研究使我们能够确认对羟基苯甲酰肼在活性位点内的优先结合模式。
• Structure-activity Relationship Studies of Microbiologically Active Thiosemicarbazides Derived from Hydroxybenzoic Acid Hydrazides
  作者：Tomasz Plech、Agata Paneth、Barbara Kaproń、Urszula Kosikowska、Anna Malm、Aleksandra Strzelczyk、Paweł Stączek

  DOI：10.1111/cbdd.12392

  日期：2015.3

  of Gram‐negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially

  合成了45种硫代氨基脲衍生物，并评估了它们对革兰氏阳性和革兰氏阴性细菌的抗菌活性。某些所述化合物对革兰氏阳性菌参考菌株表现出有趣的活性，而只有两种衍生物具有抑制革兰氏阴性菌生长的能力（大肠杆菌ATCC 25922，肺炎克雷伯菌ATCC 13883，变形杆菌）ATCC 12453）。在水杨酸酰肼衍生物的情况下观察到最有效的抗菌活性。活动的差异促使我们使用分子力学水平进行构象分析。获得的结果表明，分子的几何形状，尤其是在硫代氨基脲骨架的N4-末端，决定了抗菌活性。不幸的是，与我们的预期相反，仅一种测试的化合物抑制了topoIV酶的活性，而且它们都没有针对DNA促旋酶的活性。
• Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids
  作者：Tomasz Plech、Barbara Kaproń、Agata Paneth、Urszula Kosikowska、Anna Malm、Aleksandra Strzelczyk、Paweł Stączek、Łukasz Świątek、Barbara Rajtar、Małgorzata Polz-Dacewicz

  DOI：10.1016/j.ejmech.2015.04.058

  日期：2015.6

  A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Design and Synthesis of p-hydroxybenzohydrazide Derivatives for their Antimycobacterial Activity
  作者：Ritesh.P. Bhole、Deepak.D. Borkar、Kishore.P. Bhusari、Prashant.A. Patil

  DOI：10.5012/jkcs.2012.56.2.236

  日期：2012.4.20

  The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.

  人类的主要霉菌感染是由结核分枝杆菌引起的结核病。结核病是世界上主要的传染性死亡原因。因此，人们一直迫切需要新的和更好的结核病治疗方法。设计含有 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide 分子的新化合物的根本原因是为了获得更好的抗结核活性。QSAR 和计算机科学的最新进展为设计任何化合物的结构提供了一种系统方法，而且可以在合成前预测化合物的生物活性。我们使用 V-life MDS (3.50) 对 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide 及其衍生物进行了 3D-QSAR 研究。使用了多种统计方法，如多元线性回归（MLR）、部分最小平方回归（PLSR）、主成分回归（PCR）和 K 近邻（kNN）。kNN显示出良好的效果，交叉验证的$r^2$为0.9319，外部测试集的$r^2$为0.8561，估计标准误差为0.2195。使用 Schrodinger GLIDE 模块进行了对接研究，结果与标准异烟肼相比，对接得分很高。设计的化合物被进一步用于合成和生物学评价。对这些化合物的抗结核评价表明，(4.a)、(4.d) 和 (4.g) 是 H37RV 的强效抑制剂。