2-(3,4-dihydroxybenzylidine)hydrazinecarbothioamide | 22043-07-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(3,4-dihydroxybenzylidine)hydrazinecarbothioamide
• 英文别名: 3,4-dihydroxybenzaldehyde thiosemicarbazone；{[(3,4-dihydroxyphenyl)methylidene]amino}thiourea；2-(4,5-dihydroxybenzylidene)hydrazine-1-carbothioamide；N-(3,4-di(hydroxy)benzylidene)thiosemicarbazide；N'-[(3,4-dihydroxyphenyl)methylideneamino]carbamimidothioic acid
• CAS: 22043-07-8
• 化学式: C₈H₉N₃O₂S
• mdl: MFCD00977619
• 分子量: 211.244
• InChiKey: WJUCYWPKZJPHEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴戊烷-2,4-二酮 、 2-(3,4-dihydroxybenzylidine)hydrazinecarbothioamide 以 乙醇 为溶剂， 反应 6.0h， 以81.7%的产率得到methyl 2-{2-[(3,4-dihydroxyphenyl)methylidene]hydrazin-1-yl}-4-methyl-1,3-thiazole-5-carboxylate
  参考文献：
  名称：

  (4-烷基-5-酰基-2-噻唑)腙衍生物及其医药 用途

  摘要：

  本发明涉及式Ⅰ所示(4‑烷基‑5‑酰基‑2‑噻唑)腙衍生物及其药学上可接受的盐，药物组合物以及其在制备流感病毒神经氨酸酶抑制剂中的应用。其中，R选自：甲基、乙基、C3～C4直链或C3～C4支链烷基；R1选自：氢、C1～C2烷基、C3～C4直链或C3～C4支链烷基、三氟甲基；R2选自：氢、C1～C2烷基、C3～C7直链或C3～C7支链烷基；Y选自：氢、2‑羟基、3‑羟基、4‑羟基、2,3‑二羟基、2，4‑二羟基、2,5‑二羟基、3,4‑二羟基、3,5‑二羟基、2‑羟基‑3‑甲氧基、3‑羟基‑4‑甲氧基、4‑羟基‑3‑甲氧基、4‑羟基‑3‑乙氧基或3,4‑亚甲二氧基。

  公开号：

  CN108503604B
• 作为产物：
  描述：

  氨基硫脲 、 3,4-二羟基苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以65.7%的产率得到2-(3,4-dihydroxybenzylidine)hydrazinecarbothioamide
  参考文献：
  名称：

  发现新型溴酚-硫代氨基脲杂化物作为用于癌症的聚（ADP-核糖）聚合酶-1（PARP-1）的强效选择性抑制剂。

  摘要：

  聚（ADP-核糖）聚合酶-1（PARP-1）是抗癌药物发现的新潜在目标。设计，合成并评估了一系列作为PARP-1抑制剂的溴酚-硫代半碳杂zone杂化物的抗肿瘤活性。其中，最有前途的化合物11对PARP-2（IC50> 1000 nM）表现出优异的选择性PARP-1抑制活性（IC50 = 29.5 nM），并对SK-OV-3，Bel-7402和在体内SK-OV-3细胞异种移植模型中，HepG2癌细胞系（IC50 = 2.39、5.45和4.60μM）以及肿瘤生长的抑制作用。进一步的研究表明，化合物11通过多种抗癌机制发挥了抗肿瘤作用，包括诱导凋亡和细胞周期停滞，DNA双链断裂的细胞蓄积，DNA修复改变，抑制H2O2触发的PARylation，通过产生细胞毒性活性氧而产生的抗增殖作用以及自噬。另外，化合物11显示出良好的药代动力学特性和良好的安全性。这些观察表明，化合物11可以用作发现新的抗癌药物的先导化合物。

  DOI：

  10.1021/acs.jmedchem.8b01946

文献信息

• Synthesis, Antibacterial, Antioxidant Activity and QSAR Studies of Novel 2-Arylidenehydrazinyl-4-arylthiazole Analogues
  作者：Mohammad Sayed Alam、Junaid Uddin Ahmed、Dong-Ung Lee

  DOI：10.1248/cpb.c14-00616

  日期：——

  A novel series of 2-arylidenehydrazinyl-4-arylthiazole analogues (3a–p) was designed and synthesized in excellent yields using a rapid, simple, efficient methodology. Sixteen novel compounds were screened for in vitro antimicrobial activities against eleven bacteria, namely, Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Bacillus subtilis, Klebsiella pneumonia, Citrobacter freundii, Cronobacter sakazakii, Salmonella enteritidis, Escherichia coli, Yersinia pestis, and Pseudomonas aeruginosa. All 16 compounds showed significant anti-bacterial activities against both Gram-positive and Gram-negative bacteria. In particular, compound 3g showed potent inhibition of E. coli and K. pneumonia, compound 3i inhibited E. faecalis, compound 3n S. tythi and E. faecalis, and compound 3c E. coli and C. sakazakii. In fact, our results indicate that most of the compounds synthesized exhibit strong antibacterial activity. The qualitative structure–antibacterial activity relationships (QSAR) were studied using the physicochemical and quantum-chemical parameters of the ab initio Hartree–Fock model at the RHF/6-31G level of theory. A good qualitative correlation between predicted physicochemical parameters (log P and polar surface area (PSA)) and antibacterial activity has been found. The synthesized compounds were also evaluated for antioxidant activity. Compounds 3j, 3a and 3i exhibited the greatest antioxidant activity, with IC50 values of 0.66, 0.81, and 1.08 µM, respectively, which were comparable to that of ascorbic acid (IC50 0.87 µM). The promising antibacterial and antioxidant activities of some of these synthesized 2-arylidenehydrazinyl-4-arylthiazole derivatives, together with the results of quantum-chemical studies, could be helpful for the development of drugs to combat diseases caused by microorganisms and oxidative stress.

  设计并合成了一系列新颖的2-芳亚甲基酰肼基-4-芳基噻唑类似物（3a-p），采用了快速、简单且高效的方法，产率极佳。对十六种新型化合物进行了体外抗菌活性筛选，针对十一种细菌，包括金黄色葡萄球菌、单核细胞增生李斯特菌、粪肠球菌、枯草芽孢杆菌、肺炎克雷伯菌、弗氏柠檬酸杆菌、坂崎克罗诺杆菌、肠炎沙门氏菌、大肠埃希氏菌、耶尔森氏鼠疫杆菌和铜绿假单胞菌。所有十六种化合物均显示出对革兰氏阳性和革兰氏阴性细菌的显著抗菌活性。特别是，化合物3g对大肠埃希氏菌和肺炎克雷伯菌表现出强效抑制，化合物3i抑制粪肠球菌，化合物3n抑制肠炎沙门氏菌和粪肠球菌，化合物3c抑制大肠埃希氏菌和坂崎克罗诺杆菌。事实上，我们的结果表明，大多数合成化合物都表现出强大的抗菌活性。通过使用从头计算Hartree-Fock模型的物理化学和量子化学参数，在RHF/6-31G理论水平上研究了定性结构-抗菌活性关系（QSAR）。发现预测的物理化学参数（log P和极性表面积（PSA））与抗菌活性之间存在良好的定性相关性。合成的化合物还评估了其抗氧化活性。化合物3j、3a和3i表现出最强的抗氧化活性，IC50值分别为0.66、0.81和1.08 µM，可与抗坏血酸（IC50 0.87 µM）相媲美。这些合成的2-芳亚甲基酰肼基-4-芳基噻唑衍生物中部分化合物表现出有前景的抗菌和抗氧化活性，结合量子化学研究的结果，可能有助于开发针对由微生物和氧化应激引起的疾病的药物。
• Design, Synthesis and Biological Evaluation of Hydroxy- or Methoxy-Substituted Phenylmethylenethiosemicarbazones as Tyrosinase Inhibitors
  作者：Wei Yi、Ri-Hui Cao、Zhi-Yong Chen、Liang Yu、Lin Ma、Hua-Can Song

  DOI：10.1248/cpb.57.1273

  日期：——

  A series of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. The results demonstrated that most of target compounds had remarkable inhibitory activities on mushroom tyrosinase. Interestingly, compound 2h was found to be the most potent tyrosinase inhibitor with IC50 value of 0.18 μM. The possible interaction mode between compound 2h and tyrosinase was proposed. In addition, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities of select compounds (IC50<10.0 μM) were also investigated. Compounds 2d, 2e, 2h, 2i and 2l exhibited more potent DPPH radical scavenging activity than well-known antioxidants ascorbic acid (Vc) and tertiary butyl hydroquinone (TBHQ). These results suggested that such compounds might be utilized for the development of new candidate for treatment of dermatological disorders.

  一系列羟基或甲氧基取代的苯甲叉基硫代半卡巴脒被设计、合成并评估为蘑菇酪氨酸酶抑制剂。结果表明，大多数目标化合物对蘑菇酪氨酸酶具有显著的抑制活性。有趣的是，化合物2h被发现是最强效的酪氨酸酶抑制剂，其IC50值为0.18 μM。提出了化合物2h与酪氨酸酶之间可能的相互作用模式。此外，还研究了选定化合物（IC50<10.0 μM）的1,1-二苯基-2-苦基肼（DPPH）自由基清除活性。化合物2d、2e、2h、2i和2l表现出比已知的抗氧化剂抗坏血酸（Vc）和叔丁基对苯二酚（TBHQ）更强的DPPH自由基清除活性。这些结果表明，这些化合物可能被用于开发治疗皮肤病的新的候选药物。
• Acetic acid mediated regioselective synthesis of 2,4,5-trisubstituted thiazoles by a domino multicomponent reaction
  作者：Mohit Saroha、Jitender M. Khurana

  DOI：10.1039/c9nj01717h

  日期：——

  synthesis of novel 2,4,5-trisubstituted thiazole derivatives has been reported by a domino reaction of thiosemicarbazide and aldehydes/ketones/isatin, to generate thiosemicarbazones (in situ) followed by addition of arylglyoxal and active methylene/activated C–H acids/pyrazole/indole in ethanol at 80 °C. The products are obtained in high yields by a simple work up. Metal free, short reaction time and

  据报道，乙酸介导的新型2,4,5-三取代噻唑衍生物的区域选择性合成是通过硫代氨基脲与醛/酮/ Isatin的多米诺反应，生成硫代氨基脲（原位），然后加入芳基乙二醛和活性亚甲基/活化的C。在80°C下于乙醇中的-H酸/吡唑/吲哚。通过简单的后处理即可获得高收率的产品。无金属，反应时间短，产率高是该方法的优点。
• Synthesis, structural characterization, oxygen sensitivity, and antimicrobial activity of ruthenium(II) carbonyl complexes with thiosemicarbazones
  作者：Nurdan Öztürk、Pelin Köse Yaman、Murat Yavuz、Özlem Öter、Suna Timur、Elif Subaşi

  DOI：10.1080/00958972.2014.948433

  日期：2014.8.18

  [Ru(CO)(PPh3)2(η3-O,N3,S-TSC1)] (1), [Ru(Cl)(CO)(PPh3)2(η2-N3,S-TSC2)] (2), and [Ru(Cl)(CO)(PPh3)2(η2-N3,S-TSC3)] (3) have been prepared by reacting [Ru(H)(Cl)(CO)(PPh3)3] with the respective thiosemicarbazones TSC1 (2-hydroxy-3-methoxybenzaldehyde thiosemicarbazone), TSC2 (3-hydroxybenzaldehyde thiosemicarbazone), and TSC3 (3,4-dihydroxybenzaldehyde thiosemicarbazone) in a 1 : 1 M ratio in toluene

  [Ru(CO)(PPh3)2(η3-O,N3,S-TSC1)] (1), [Ru(Cl)(CO)(PPh3)2(η2-N3,S-TSC2)] (2) , 和 [Ru(Cl)(CO)(PPh3)2(η2-N3,S-TSC3)] (3) 是通过 [Ru(H)(Cl)(CO)(PPh3)3] 与在甲苯和所有复合物中以 1:1 M 比​​例的相应缩氨基硫脲 TSC1（2-羟基-3-甲氧基苯缩硫脲）、TSC2（3-羟基苯甲醛缩氨基硫脲）和 TSC3（3,4-二羟基苯甲醛缩氨基硫脲）的特征在于UV-vis、FT-IR 和 1H 和 31P NMR 光谱。光谱研究表明，TSC1 作为三齿配体与中心金属配位，通过偶氮甲碱氮 (C=N)、酚氧和硫与 1 中的钌配位，而 TSC2 和 TSC3 作为双齿配体与钌配位偶氮甲碱氮 (C=N) 和硫在 2 和 3 中。已确定 1-3 和 [Ru(Cl)(CO)(PPh3)2(η2-N3
• Discovery of New Hydrazone-Thiazole Polyphenolic Antioxidants through Computer-Aided Design and In Vitro Experimental Validation
  作者：Gabriel Marc、Anca Stana、Mihaela Tertiş、Cecilia Cristea、Alexandra Ciorîţă、Ștefan-Mihai Drăgan、Vlad-Alexandru Toma、Raluca Borlan、Monica Focșan、Adrian Pîrnău、Laurian Vlase、Smaranda Oniga、Ovidiu Oniga

  DOI：10.3390/ijms241713277

  日期：——

  Oxidative stress is linked to a series of diseases; therefore, the development of efficient antioxidants might be beneficial in preventing or ameliorating these conditions. Based on the structure of a previously reported compound with good antioxidant properties and on computational studies, we designed several catechol derivatives with enhanced antioxidant potential. The compounds were synthesized and physicochemically characterized, and their antioxidant activity was assessed through different antiradical, electron transfer and metal ions chelation assays, their electrochemical behavior and cytotoxicity were studied. The results obtained in the in vitro experiments correlated very well with the in silico studies; all final compounds presented very good antioxidant properties, generally superior to those of the reference compounds used. Similarly, the results obtained from studying the compounds’ electrochemical behavior were in good agreement with the results of the antioxidant activity evaluation assays. Regarding the compounds’ cytotoxicity, compound 7b had a dose-dependent inhibitory effect against all cell lines. In conclusion, through computer-aided design, we developed several catechol thiazolyl-hydrazones with excellent antioxidant properties, of which compound 7b, with two catechol moieties in its structure, exhibited the best antioxidant activity.

  氧化应激与一系列疾病有关；因此，开发高效的抗氧化剂可能有利于预防或改善这些疾病。基于之前报道的一种具有良好抗氧化性的化合物的结构和计算研究，我们设计了几种具有更强抗氧化潜力的儿茶酚衍生物。我们合成了这些化合物并对其进行了物理化学表征，通过不同的抗自由基、电子传递和金属离子螯合实验评估了它们的抗氧化活性，还研究了它们的电化学行为和细胞毒性。体外实验所获得的结果与硅学研究结果有很好的相关性；所有最终化合物都具有很好的抗氧化性，总体上优于所使用的参考化合物。同样，化合物的电化学行为研究结果与抗氧化活性评估实验结果也非常吻合。在化合物的细胞毒性方面，化合物 7b 对所有细胞株都有剂量依赖性抑制作用。总之，通过计算机辅助设计，我们开发出了几种具有优异抗氧化性能的儿茶酚噻唑肼类化合物，其中化合物 7b 的结构中有两个儿茶酚分子，其抗氧化活性最佳。