2-(4-hydroxybenzoyl)-N-phenylhydrazincarbothioamide | 26036-25-9

• 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: 2-(4-hydroxybenzoyl)-N-phenylhydrazincarbothioamide
• 英文别名: N-phenyl-2-(4-hydroxybenzoyl)hydrazinocarbothioamid；1-(4-hydroxybenzoyl)-4-phenylthiosemicarbazide；1-hydroxybenzoyl-4-phenyl-3-thiosemicarbazide；C6H5NHCSNHNHCOC6H4-p-OH；1-(4-hydroxy-benzoyl)-4-phenyl thiosemicarbazide；1-(4-Hydroxy-benzoyl)-4-phenyl-thiosemicarbazid；1-[(4-Hydroxybenzoyl)amino]-3-phenylthiourea
• CAS: 26036-25-9
• 化学式: C₁₄H₁₃N₃O₂S
• 分子量: 287.342
• InChiKey: YQIYQBBSEBSNQH-UHFFFAOYSA-N

物化性质

• 熔点：
  206 °C
• 密度：
  1.395±0.06 g/cm3(Predicted)
• 溶解度：
  33 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 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：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-hydroxybenzoyl)-N-phenylhydrazincarbothioamide 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 5-(4-Hydroxyphenyl)-4-phenyl-2-[(4-phenylpiperazin-1-yl)methyl]-1,2,4-triazole-3-thione
  参考文献：
  名称：

  Synthesis and Tuberculostatic Activity of Some 2-Piperazinmethylene Derivatives 1,2,4-Triazole-3-Thiones

  摘要：

  The Mannich. reaction's products of 1,2,4-triazole-3-thiones, substituted in position 4 (with ethyl, allyl, phenyl, Ph-4-Br) or 5 (with phenyl, Ph-4-OH, Ph-3,4,5-(OMe)(3), 2-phenyl) were obtained. Their amino-components were 1-phenylpiperazine, 1-(4-fluorophenyl)-piperazine, 1-benzylpiperazine, 1-(2-pyridyl)-piperazine and 1-piperonyl-piperazine. Tuberculostatic activity of the compounds obtained was tested in vitro and their MIC values within 25-100 mcg/mL.

  DOI：

  10.1080/104265090517280
• 作为产物：
  描述：

  过氧化氢酶 在 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 2-(4-hydroxybenzoyl)-N-phenylhydrazincarbothioamide
  参考文献：
  名称：

  Mn(II) 催化合成 5(4-羟基苯基)-2-(N-苯基氨基)-1,3,4-恶二唑：晶体结构、DFT、分子对接、Hirshfeld 表面分析和对 DL 细胞的体外抗癌活性

  摘要：

  新型合成分子的合成和筛选作为治疗癌症的潜在治疗剂受到关注。在本研究中，合成了一种新化合物 5(4-羟基苯基)-2-(N-苯基氨基)-1,3,4-恶二唑 (Hppo)，并研究了其对道尔顿淋巴瘤 (DL) 肿瘤细胞的抗癌活性来源于鼠 T 细胞淋巴瘤。Hppo 已通过 IR、NMR 和单晶 X 射线数据进行表征。Hppo 的结构通过氢键相互作用而稳定，并在空间群为 P bc n 的正交系统中结晶。与 Hirshfeld 表面分析相关的指纹图表明存在不同类型的弱相互作用，即。CH…N、OH…N 和 CH…O。还进行了 DFT 计算以验证 Hppo 的理化性质, 获得的结果与实验结果非常吻合。Hppo 的 7.344 eV 的 HOMO 和 LUMO 能隙表明良好的 NLO 特性。使用 MTT 法测试了 Hppo 对道尔顿淋巴瘤细胞的细胞毒性活性，结果表明该化合物显示出令人钦佩的抗癌活性 (IC 50=

  DOI：

  10.1016/j.molstruc.2021.131547

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。
• Design and Synthesis of Some New 1,3,4-Thiadiazines with Coumarin Moieties and Their Antioxidative and Antifungal Activity
  作者：Milan Čačić、Valentina Pavić、Maja Molnar、Bojan Šarkanj、Elizabeta Has-Schön

  DOI：10.3390/molecules19011163

  日期：——

  A series of newly disubstituted (compounds 4a,b) and trisubstituted 1,3,4-thiadiazines 5a–l with various substituents was prepared utilizing different thiosemicarbazides and 3-α-bromoacetylcoumarins as starting compounds. The structures of the synthesized 1,3,4-thiadiazines are elucidated and confirmed utilizing the corresponding analytical and spectroscopic data. All of the new thiadiazine derivatives were tested for their antioxidant activity, employing different antioxidant assays (DPPH scavenging activity, iron chelating activity, power reducing activity). Compounds 5b, 5f, 5j and 4b were proven to be the best DPPH radical scavengers, while compounds 5h and 5j have shown the best iron chelating activity. Thiadiazine derivatives were also tested on their antifungal activity against four mycotoxicogenic fungi, Aspergillus flavus, A. ochraceus, Fusarium graminearum and F. verticillioides. The best antifungal against A. flavus was proven to be compound 5e, while compounds 4a and 5c were the best antifungals on A. ochraceus, and compound 5g showed the best antifungal activity on F. verticillioides.

  一系列新合成的二取代（化合物4a,b）和三取代的1,3,4-噻二嗪化合物5a–l，采用不同的硫代氨基脲和3-α-溴乙酰香豆素作为起始化合物进行制备。利用相应的分析和光谱数据阐明并确认了合成的1,3,4-噻二嗪的结构。所有的新噻二嗪衍生物均进行了抗氧化活性的测试，采用不同的抗氧化测定方法（DPPH清除活性、铁螯合活性、还原能力）。化合物5b、5f、5j和4b被证实为最佳的DPPH自由基清除剂，而化合物5h和5j显示出最佳的铁螯合活性。噻二嗪衍生物还被测试其对四种产霉毒素真菌的抗真菌活性，包括黄曲霉、鼠尾草霉、镰刀菌及旋链镰刀菌。化合物5e被证明对黄曲霉具有最佳的抗真菌活性，化合物4a和5c是对鼠尾草霉的最佳抗真菌剂，而化合物5g在旋链镰刀菌上显示出最佳的抗真菌活性。
• A KHSO4 mediated facile synthesis of 2-amino-1,3,4-oxadiazole derivatives
  作者：Binyu Long、Binghua Tian、Qiang Tang、Xiangnan Hu、Lei Han、Zifan Wang、Chenyu Wang、Yue Wu、Yu Yu、Zongjie Gan

  DOI：10.1016/j.tet.2021.132382

  日期：2021.9

  A novel, efficient and mild KHSO4 mediated synthesis for 2-amino-1,3,4-oxadiazoles has been established via the cyclodesulfurization of benzoylhydrazine and isothiocyanate derivatives in one pot. The reactions proceeded smoothly at room temperature and produced corresponding products in moderate to good yields. This protocol also showed good functional group tolerance.

  通过苯甲酰肼和异硫氰酸酯衍生物的环化脱硫，建立了一种新型、高效且温和的 KHSO 4介导的 2-氨基-1,3,4-恶二唑合成方法。反应在室温下顺利进行，并以中等至良好的收率产生相应的产物。该协议还显示出良好的官能团耐受性。
• 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。