2-(2,6-dichlorobenzylidene)hydrazinecarbothioamide | 24047-22-1

• 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-(2,6-dichlorobenzylidene)hydrazinecarbothioamide
• 英文别名: 2-(2,6-dichlorobenzylidene)hydrazinocarbothioamide；2,6-dichloro-benzaldehyde-thiosemicarbazone；2,6-Dichlor-benzaldehyd-thiosemicarbazon；2,6-Dichlorbenzaldehyd-thiosemicarbazon；Hydrazinecarbothioamide, 2-[(2,6-dichlorophenyl)methylene]-, (E)-；[(2,6-dichlorophenyl)methylideneamino]thiourea
• CAS: 24047-22-1
• 化学式: C₈H₇Cl₂N₃S
• mdl: MFCD00136202
• 分子量: 248.136
• InChiKey: JWTQZQFPOKSWPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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：
  82.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2,6-dichlorobenzylidene)hydrazinecarbothioamide 在 iron(III) chloride 作用下， 以 乙醇 为溶剂， 以72.2%的产率得到2-氨基-5-(2,6-二氯苯基)-1,3,4-噻二唑
  参考文献：
  名称：

  新型 4-噻唑烷酮类作为丙型肝炎病毒 NS5B RNA 依赖性 RNA 聚合酶的非核苷抑制剂

  摘要：

  为了继续努力开发新的衍生物作为丙型肝炎病毒 (HCV) NS5B 抑制剂，我们合成了新的 5-亚芳基-4-噻唑烷酮。测试了新化合物 29-42 及其合成前体 22-28 的 HCV NS5B 抑制活性；其中 12 种化合物的 IC50 值介于 25.3 和 54.1 µM 之间。化合物 33 是​​一种亚芳基衍生物，被发现是该系列中活性最高的化合物，IC50 值为 25.3 µM。对 NS5B 的拇指口袋 II 进行了分子对接研究，以假设这些化合物的结合模式。

  DOI：

  10.1002/ardp.201400247
• 作为产物：
  描述：

  2,6-二氯苯甲醛 、 氨基硫脲 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 以27%的产率得到2-(2,6-dichlorobenzylidene)hydrazinecarbothioamide
  参考文献：
  名称：

  新型 4-噻唑烷酮类作为丙型肝炎病毒 NS5B RNA 依赖性 RNA 聚合酶的非核苷抑制剂

  摘要：

  为了继续努力开发新的衍生物作为丙型肝炎病毒 (HCV) NS5B 抑制剂，我们合成了新的 5-亚芳基-4-噻唑烷酮。测试了新化合物 29-42 及其合成前体 22-28 的 HCV NS5B 抑制活性；其中 12 种化合物的 IC50 值介于 25.3 和 54.1 µM 之间。化合物 33 是​​一种亚芳基衍生物，被发现是该系列中活性最高的化合物，IC50 值为 25.3 µM。对 NS5B 的拇指口袋 II 进行了分子对接研究，以假设这些化合物的结合模式。

  DOI：

  10.1002/ardp.201400247

文献信息

• Synthesis, Characterization, and Molecular Docking of Novel <i>bis</i> -thiazolyl Thienothiophene Derivatives as Promising Cytotoxic Antitumor Drug
  作者：Sobhi M. Gomha、Maher A. El-Hashash、Mastoura M. Edrees、Elham Ezz El-Arab

  DOI：10.1002/jhet.2869

  日期：2017.9

  A novel, facile reaction for the synthesis of series of bis‐thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and bis‐2‐bromoacetylthieno[2,3‐b]thiophene derivatives in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, and 1H and 13C NMR) and elemental analyses. Fifteen

  通过适当的硫代半脲酮衍生物与双-2-溴代乙酰基噻吩并[2,3- b ]噻吩衍生物在乙醇中回流下的反应，已经开发出一种新颖，简便的合成双噻唑衍生物系列的方法。新合成产物的结构是根据光谱数据（质量，IR和1 H和131 H NMR）和元素分析。评价了合成化合物中的十五种化合物对人肝肝癌细胞系（HepG2）的抗癌活性。所有化合物均显示出抗癌活性，但效力与参考药物顺铂相当。此外，使用MOE软件进行的分子对接研究预测了活性最高的化合物5o与人类热休克蛋白90的活性位点之间的最佳结合方式。计算研究证实了生物学活性的结果。
• Synthesis of Some Novel 1,4-Phenylene-<i>bis</i>-thiazolyl Derivatives and Their Anti-hypertensive α-blocking Activity Screening
  作者：Fathy M. Abdelrazek、Sobhi M. Gomha、Peter Metz、Mohamed M. Abdalla

  DOI：10.1002/jhet.2633

  日期：2017.1

  A series of novel 1,4‐phenylene‐bis‐thiazolyl derivatives were synthesized and evaluated for their anti‐hypertensive activities as α‐blocking agents and some of them showed promising activities.

  合成了一系列新颖的1,4-亚苯基-双-噻唑基衍生物，并评估了它们作为α-阻滞剂的抗高血压活性，其中一些显示出良好的活性。
• Antihypertensive thiadiazoles. 1. Synthesis of some 2-aryl-5-hydrazino-1,3,4-thiadiazoles with vasodilator activity
  作者：Stephen Turner、Malcolm Myers、Brian Gadie、Anthony J. Nelson、Robin Pape、John F. Saville、John C. Doxey、Timothy L. Berridge

  DOI：10.1021/jm00400a003

  日期：1988.5

  with a 2-substituted phenyl ring had higher activity than their 3- or 4-substituted counterparts or those containing heteroaryl groups. The 2-methylphenyl and 2-ethylphenyl derivatives 7 and 18 were the most potent members of the series. Preliminary studies indicated that the hypotensive action of these compounds was due to a direct relaxant effect on vascular smooth muscle.

  已经合成了一些2-芳基-5-肼基-1,3,4-噻二唑并筛选了其降压活性。通常，具有2-取代的苯环的化合物比其3-或4-取代的对应物或含有杂芳基的化合物具有更高的活性。2-甲基苯基和2-乙基苯基衍生物7和18是该系列中最有效的成员。初步研究表明，这些化合物的降压作用归因于对血管平滑肌的直接松弛作用。
• 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。
• Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones
  作者：Hasnain Mehmood、Mustapha Musa、Simon Woodward、Md Shahadat Hossan、Tracey D. Bradshaw、Muhammad Haroon、Andrew Nortcliffe、Tashfeen Akhtar

  DOI：10.1039/d2ra03226k

  日期：——

  concentrations. Cell cycle, caspase activation and Western blot assays demonstrated that compounds 3b′ and 3f induce cancer cell death via caspase-dependent apoptosis. The combination of straight forward synthesis and high activity makes the thiazoles 3 an interesting lead for further development.

  取代的缩氨基硫脲与 α-溴-4-氰基苯乙酮的环化允许快速单步可持续合成 4-氰基苯基-2-肼基噻唑文库（30 个例子，66-79%）。所有都显示出对 HCT-116 和 MCF-7 癌细胞系的抗癌功效，其中大多数比顺铂阳性对照更具活性。化合物 2-(2-(2-hydroxy-3-methylbenzylidene)hydrazinyl)-4-(4-cyanophenyl)thiazole ( 3f ) 和 2-(2-((pentafluorophenyl)methylene)-hydrazinyl)-4-(4 -氰基苯基)噻唑 ( 3a' ) 显示出针对 MCF-7 乳腺癌细胞的最佳 GI 50值（1.0 ± 0.1 μM 和 1.7 ± 0.3 μM）。抗结直肠癌HCT-116细胞，(2-(2-(3-bromothiophen-2-yl)methylene)hydrazinyl)-4-(