2-([1,1'-biphenyl]-4-ylmethylene)hydrazine-1-carbothioamide

• 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-([1,1'-biphenyl]-4-ylmethylene)hydrazine-1-carbothioamide
• 英文别名: 2-((1,1'-biphenyl)-4-ylmethylidene)hydrazinocarbothioamide；2-(biphenyl-4-ylmethylidene)hydrazinecarbothioamide；[(4-Phenylphenyl)methylideneamino]thiourea
• 化学式: C₁₄H₁₃N₃S
• mdl: MFCD01740433
• 分子量: 255.343
• InChiKey: ZGTAYOMAARHFLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-([1,1'-biphenyl]-4-ylmethylene)hydrazine-1-carbothioamide 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以63%的产率得到5-([1,1'-biphenyl]-4-yl)-1,3,4-thiadiazol-2-amine
  参考文献：
  名称：

  可重复使用的硅键合钌络合物的分子内环化的光氧化还原催化。

  摘要：

  通过使用稳定的，可重复使用的二氧化硅结合的生色团进行光氧化还原催化，对一系列2-苄叉肼肼甲硫基酰胺进行分子内环化，得到5-苯基-1,3,4-噻二唑-2-胺。通过碳二亚胺介导的市售胺官能化二氧化硅珠与羧酸官能化钌配合物的偶联，可以轻松制备该催化剂。固定的催化剂易于通过过滤从反应产物中除去，并且使用八次而不会损失催化活性。这种简单，安全和实用的方法是常规程序的一种有吸引力的替代方法。

  DOI：

  10.1002/cctc.201500304
• 作为产物：
  描述：

  氨基硫脲 、 对苯基苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以75%的产率得到2-([1,1'-biphenyl]-4-ylmethylene)hydrazine-1-carbothioamide
  参考文献：
  名称：

  GlcN-6-P合酶的2-氨基-4-甲基噻唑类似物抑制剂的合理设计，合成和抗菌研究。

  摘要：

  通过三步反应开发了一系列新颖的2-氨基-4-甲基噻唑类似物，其中包括肼-1-羧酰亚胺酰胺基序，以对抗革兰氏阳性和革兰氏阴性细菌和真菌感染。值得注意的是，与对哺乳动物细胞毒性极低的参考药物相比，噻唑-羧酰亚胺酰胺衍生物4a-d显示出出色的抗菌活性和最有效的类似物4d，MIC / MBC值为0.5和4μg/ mL。超过100倍。显微镜研究了4d联苯类似物，显示了细胞壁裂解并通过破坏细菌膜促进了快速杀菌活性。另外，进行了针对GlcN-6-P合酶抑制的有趣的体外研究，该研究显示了在纳摩尔范围内的效力。与此同时，这是第一项采用仿生策略设计可靶向GlcN-6-P合酶作为抗菌剂的有效噻唑-羧二酰亚胺的研究。重要的是，对活性最强的4d类似物进行了分子建模仿真，以研究该类似物的相互作用，该相互作用对支持体外数据的葡糖胺结合位点显示出良好的结合倾向。

  DOI：

  10.1016/j.bioorg.2020.103781

文献信息

• The rational design, synthesis, and antimicrobial investigation of 2-Amino-4-Methylthiazole analogues inhibitors of GlcN-6-P synthase
  作者：Abdelsattar M. Omar、Saleh Ihmaid、EL-Sayed E. Habib、Sultan S. Althagfan、Sahar Ahmed、Hamada S. Abulkhair、Hany E.A. Ahmed

  DOI：10.1016/j.bioorg.2020.103781

  日期：2020.6

  A series of novel 2-Amino-4-Methylthiazole analogs were developed via three-step reaction encompassing hydrazine-1-carboximidamide motif to combat Gram-positive and Gram-negative bacterial and fungal infections. Noticeably, the thiazole-carboximidamide derivatives 4a-d displayed excellent antimicrobial activity and the most efficacious analogue 4d with MIC/MBC values of 0.5 and 4 μg/mL, compared to

  通过三步反应开发了一系列新颖的2-氨基-4-甲基噻唑类似物，其中包括肼-1-羧酰亚胺酰胺基序，以对抗革兰氏阳性和革兰氏阴性细菌和真菌感染。值得注意的是，与对哺乳动物细胞毒性极低的参考药物相比，噻唑-羧酰亚胺酰胺衍生物4a-d显示出出色的抗菌活性和最有效的类似物4d，MIC / MBC值为0.5和4μg/ mL。超过100倍。显微镜研究了4d联苯类似物，显示了细胞壁裂解并通过破坏细菌膜促进了快速杀菌活性。另外，进行了针对GlcN-6-P合酶抑制的有趣的体外研究，该研究显示了在纳摩尔范围内的效力。与此同时，这是第一项采用仿生策略设计可靶向GlcN-6-P合酶作为抗菌剂的有效噻唑-羧二酰亚胺的研究。重要的是，对活性最强的4d类似物进行了分子建模仿真，以研究该类似物的相互作用，该相互作用对支持体外数据的葡糖胺结合位点显示出良好的结合倾向。
• Novel molecular discovery of promising amidine-based thiazole analogues as potent dual Matrix Metalloproteinase-2 and 9 inhibitors: Anticancer activity data with prominent cell cycle arrest and DNA fragmentation analysis effects
  作者：Abdelsattar M. Omar、Jürgen Bajorath、Saleh Ihmaid、Hany M. Mohamed、Ahmed M. El-Agrody、Ahmed Mora、Moustafa E. El-Araby、Hany E.A. Ahmed

  DOI：10.1016/j.bioorg.2020.103992

  日期：2020.8

  Thiazole derivatives are known to possess various biological activities such as antiparasitic, antifungal, anti-microbial and antiproliferative activities. Matrix metalloproteinases (MMPs) are important protease target in-volved in tumor progression including angiogenesis, tissue invasion, and migration. Therefore, MMPs have also been reported as potential diagnostic and prognostic biomarkers in many types of cancer. Herein, new aryl thiazoles were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines including the invasive MDA-MB-231 line. Some of these compounds showed IC50 values in the submicromolar range in anti -proliferative assays. In order to examine the relationship between their anticancer activity and MMPs targets, the compounds were evaluated for their inhibitory effects on MMP-2 and 9. That data obtained revealed that most of these compounds were potent dual MMP-2/9 inhibitors at nanomolar concentrations. Among these, 2-(1-(2-(2-((E)-4-iodobenzylidene)hydrazineyl)-4-methylthiazol-5-yl)ethylidene)hydrazine-1-carboximidamide (4a) was the most potent non-selective dual MMP-2/9 inhibitor with inhibitory concentrations of 56 and 38 nM re-spectively. When compound 4a was tested in an MDA-MB-231, HCT-116, MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibit cell migration, and suppressed cell cycle pro-gression leading to DNA fragmentation. Taken together, the results of our studies indicate that the newly dis-covered thiazole-based MMP-2/9 inhibitors have significant potential for anticancer treatment.
• 10.17179/excli2017-208
  作者：Gabr, Moustafa T.、El-Gohary, Nadia S.、El-Bendary, Eman R.、El-Kerdawy, Mohamed M.、Ni, Nanting

  DOI：10.17179/excli2017-208

  日期：——
• Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
  作者：Thiago M. de Aquino、Paulo H. B. França、Érica E. E. S. Rodrigues、Igor. J.S. Nascimento、Paulo F. S. Santos-Júnior、Pedro G. V. Aquino、Mariana S. Santos、Aline C. Queiroz、Morgana V. Araújo、Magna S. Alexandre-Moreira、Raiza R. L. Rodrigues、Klinger A. F. Rodrigues、Johnnatan D. Freitas、Jacques Bricard、Mario R. Meneghetti、Jean-Jacques Bourguignon、Martine Schmitt、Edeildo F. da Silva-Júnior、João X. de Araújo-Júnior

  DOI：10.2174/1573406417666210216154428

  日期：2022.2

  Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi.

  Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds.

  A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software.

  The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms.

  The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。
• Photoredox Catalysis of Intramolecular Cyclizations with a Reusable Silica-Bound Ruthenium Complex
  作者：Gregory J. Barbante、Trent D. Ashton、Egan H. Doeven、Frederick M. Pfeffer、David J. D. Wilson、Luke C. Henderson、Paul S. Francis

  DOI：10.1002/cctc.201500304

  日期：2015.6.1

  Photoredox catalysis with the use of a stable, reusable silica‐bound chromophore was applied to the intramolecular cyclization of a series of 2‐benzylidenehydrazinecarbothioamides to give 5‐phenyl‐1,3,4‐thiadiazol‐2‐amines. The catalyst was readily prepared by carbodiimide‐mediated coupling of commercially available amine‐functionalized silica beads to a carboxylic acid functionalized ruthenium complex

  通过使用稳定的，可重复使用的二氧化硅结合的生色团进行光氧化还原催化，对一系列2-苄叉肼肼甲硫基酰胺进行分子内环化，得到5-苯基-1,3,4-噻二唑-2-胺。通过碳二亚胺介导的市售胺官能化二氧化硅珠与羧酸官能化钌配合物的偶联，可以轻松制备该催化剂。固定的催化剂易于通过过滤从反应产物中除去，并且使用八次而不会损失催化活性。这种简单，安全和实用的方法是常规程序的一种有吸引力的替代方法。