2-乙酰基吡啶-(4-苯基缩氨基硫脲) | 63698-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-乙酰基吡啶-(4-苯基缩氨基硫脲)
• 英文名称: 2-acetylpyridine-(4-phenylthiosemicarbazone)
• 英文别名: (E)-N-phenyl-2-(1-(pyridin-2-yl)ethylidene)hydrazine-1-carbothioamide；1-phenyl-3-[(E)-1-(2-pyridyl)ethylideneamino]thiourea；1-phenyl-3-[(E)-1-pyridin-2-ylethylideneamino]thiourea
• CAS: 63698-06-6
• 化学式: C₁₄H₁₄N₄S
• 分子量: 270.358
• InChiKey: VHVSCHSQNUUXNS-GZTJUZNOSA-N

物化性质

• 熔点：
  190-192 °C(Solv: ethanol (64-17-5))
• 沸点：
  418.1±37.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-乙酰基吡啶-(4-苯基缩氨基硫脲) 在 sodium perchlorate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 24.0h， 生成 2-acetylpyridine-N(4)-phenylthiosemicarbazone
  参考文献：
  名称：

  具有生物活性的硫半脲铁螯合剂及其与亚铁胺B和EDTA铁的反应；动力学研究†

  摘要：

  中的Fe III选自Fe抽象III / DFO和Fe III / EDTA复合物系统由衍生自缩氨基硫脲配位体2-乙酰基吡啶已从动力学力学的角度在相关的pH条件下以及在不同的温度和缓冲溶液中进行了研究。已经发现反应极其依赖于反应介质中存在的TSC配体的主要E / Z异构形式。因此，还已经在等效条件下监测了在游离配体上发生的异构化过程。尽管在所使用的条件下没有质子化，但发现异构化过程是依赖于酸的，并且大概通过配体的偶氮型互变异构体。在所有情况下，都已建立了外层相互作用过程的存在，既促进了反应又产生了末端复合物。已经发现，配体的取向更好的形式（EZ硫醇盐）与[Fe（HDFO）] +络合物反应更快，尽管对于单N 4取代的硫代半碳氮杂烷，该过程因形成末端外环而受阻。复杂的领域。与从[Fe（EDTA）（H 2 O）]中提取Fe III的比较- 在动力学特征上存在显着差异，甚至暗示了最不适合直接络合的异

  DOI：

  10.1039/c1dt11685a
• 作为产物：
  描述：

  硫代异氰酸苯酯 在 hydrazine hydrate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 2-乙酰基吡啶-(4-苯基缩氨基硫脲)
  参考文献：
  名称：

  Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents

  摘要：

  In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 mu M, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial-mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112349

文献信息

• Gold complexes with thiosemicarbazones: reactions of bi- and tridentate thiosemicarbazones with dichloro[2-(dimethylaminomethyl)phenyl-C 1,N ]gold(III), [Au(damp-C 1,N )Cl2]
  作者：Ulrich Abram、Kirstin Ortner、Ronald Gust、Klaus Sommer

  DOI：10.1039/a908712e

  日期：——

  Dichloro[2-(N,N-dimethylaminomethyl)phenyl-C1,N]gold(III), [Au(damp-C1,N)Cl2] (1), reacts with salicylaldehyde thiosemicarbazone (H2saltsc), vanilline thiosemicarbazone (Hvantsc), N-methylpyrrole aldehyde thiosemicarbazone (Hmepyrtsc), pyridoxal methylthiosemicarbazone (H2pydoxmetsc), 2-diphenylphosphinobenzaldehyde thiosemicarbazone (HPtsc) or variously substituted acetylpyridine thiosemicarbazones (HapRtsc; R = H, Me, Ph) with cleavage of the Au–N bond and protonation of the dimethylamino group. Compounds of general formulae [Au(Hdamp-C1)Cl(L)]+ (L = Hsaltsc−, vantsc−, mepyrtsc−), [Au(Hdamp-C1)Cl(L)]2+ (L = H2pydoxmetsc) or [Au(Hdamp-C1)(L)]2+ (L = Ptsc−, apRtsc−, R = H, Me, Ph) have been isolated and characterized. The presence of the σ-bonded 2-(dimethylaminomethyl)phenyl ligand is mandatory to prevent reduction of the gold(III) centre. The crystal structures of [Au(Hdamp-C1)Cl(Hsaltsc)](PF6) (3a), [Au(Hdamp-C1)Cl(mepyrtsc)]Cl (3c), [Au(Hdamp-C1)Cl(H2pydoxmetsc)]Cl2·MeOH (4), [Au(Hdamp-C1)(apPhtsc)]Cl2·2 MeOH (5c) and [Au(Hdamp-C1)(Ptsc)]Cl2· 1.5MeOH (6) have been elucidated, showing the gold atoms in distorted square-planar co-ordination environments. The potentially O,N,S-tridentate ligands H2saltsc and H2pydoxmetsc co-ordinate in a bidentate fashion and do not incorporate the OH groups in the chelating framework, whereas HapRtsc or HPtsc co-ordinate in a tridentate manner. Generally, one or more hydrogen atoms of the heterocyclic ligands and/or the NMe2H+ group form hydrogen bridges in the solid state structures. The preliminary results of antiproliferation tests on tumor cells demonstrate the considerable cytotoxicity of these new gold complexes. p

  二氯[2-(N,N-二甲氨基甲基)苯-C1,N]金(III), [Au(damp-C1,N)Cl2] (1), 与水杨醛缩氨基硫脲(H2saltsc), 香草醛缩氨基硫脲(Hvantsc), N-甲基吡咯醛缩氨基硫脲(Hmepyrtsc), 吡哆醛缩甲基氨基硫脲(H2pydoxmetsc), 2-二苯基膦基苯甲醛缩氨基硫脲(HPtsc)或者各种取代的乙酰吡啶缩氨基硫脲(HapRtsc; R = H, Me, Ph)反应, 导致Au–N键断裂并使二甲氨基质子化. 根据通式[Au(Hdamp-C1)Cl(L)]+(L = Hsaltsc−, vantsc−, mepyrtsc−), [Au(Hdamp-C1)Cl(L)]2+(L = H2pydoxmetsc), 或者[Au(Hdamp-C1)(L)]2+(L = Ptsc−, apRtsc−, R = H, Me, Ph)分离并表征得到化合物. 为了防止金(III)中心的还原, 必须存在σ键合的2-(二甲氨基甲基)苯配体. 通过测定[Au(Hdamp-C1)Cl(Hsaltsc)](PF6) (3a), [Au(Hdamp-C1)Cl(mepyrtsc)]Cl (3c), [Au(Hdamp-C1)Cl(H2pydoxmetsc)]Cl2·MeOH (4), [Au(Hdamp-C1)(apPhtsc)]Cl2·2 MeOH (5c)和[Au(Hdamp-C1)(Ptsc)]Cl2· 1.5MeOH (6)的晶体结构, 发现金原子处于扭曲的平面四边形配位环境. 潜在的O,N,S-三齿配体H2saltsc和H2pydoxmetsc以二齿的形式配位, 没有把羟基包含在螯合骨架中, 然而HapRtsc或HPtsc以三齿的形式配位. 通常, 杂环配体的一个或者多个氢原子和/或者NMe2H+形成氢键出现在固态结构中. 对肿瘤细胞的抗增殖试验的初步结果表明这些新金配合物具有较大的细胞毒性.
• 2-Acetylpyridine Thiosemicarbazones are Potent Iron Chelators and Antiproliferative Agents: Redox Activity, Iron Complexation and Characterization of their Antitumor Activity
  作者：Des R. Richardson、Danuta S. Kalinowski、Vera Richardson、Philip C. Sharpe、David B. Lovejoy、Mohammad Islam、Paul V. Bernhardt

  DOI：10.1021/jm801585u

  日期：2009.3.12

  to the most effective HBpT and HDpT ligands. The HApT Fe complexes had the lowest FeIII/II redox potentials of any thiosemicarbazone series we have generated. This property, in combination with their ability to effectively chelate cellular Fe, make the HApT series one of the most potent antiproliferative agents developed by our group.

  通过对2-苯甲酰基吡啶硫代半碳a（HBpT），2-（3-硝基苯甲酰基）吡啶硫代半碳（（HNBpT）和二吡啶基酮硫代半碳（（HDpT）系列铁（Fe）螯合剂的系统结构活性研究，我们确定了形成Fe螯合剂所必需的结构特征配合物有效的抗癌活性（药物化学杂志。2007年，50，3716-3729）。在这项研究中，我们产生了相关的2-乙酰基吡啶硫半碳zone（HApT）类似物，以检查甲基对亚胺碳的影响。六个HApT螯合剂中的四个具有强大的抗肿瘤活性（IC 50：0.001-0.002μM）和Fe螯合功效，与最有效的HBpT和HDpT配体相似。HApT铁络合物的Fe III / II含量最低我们产生的任何硫代半碳carb系列的氧化还原电势。这种特性与有效螯合细胞铁的能力相结合，使HApT系列成为我们小组开发的最有效的抗增殖剂之一。
• [EN] CHEMICAL ACTIVATORS OF NICOTINAMIDE MONONUCLEOTIDE ADENLYLY TRANSFERASE 2 (NMNAT2) AND USES THEREOF<br/>[FR] ACTIVATEURS CHIMIQUES DE MONONUCLÉOTIDE DE NICOTINAMIDE ADÉNYLYL TRANSFÉRASE 2 (NMNAT2) ET LEURS UTILISATIONS
  申请人：UNIV TSINGHUA

  公开号：WO2020107221A1

  公开（公告）日：2020-06-04

  The present application relates to novel semicarbazones and thiosemicarbazones, to processes for preparing them, to pharmaceutical preparations comprising them, to the use of the novel semicarbazones and thiosemicarbazones for treatment and/or prophylaxis of diseases and to the use thereof for production of a medicament for treatment and/or prophylaxis of diseases, especially of neurodegeneration and age-associated diseases or conditions associated with NAD loss. The present application also provides a method for high throughput screening of NMNAT2 activators.

  本申请涉及新型半胱氨酮和硫代半胱氨酮，以及制备它们的方法，包括含有它们的药物制剂，以及利用新型半胱氨酮和硫代半胱氨酮治疗和/或预防疾病的用途，以及用于生产治疗和/或预防疾病的药物的用途，特别是神经退行性疾病和与NAD损失相关的老年疾病或状况。本申请还提供了一种高通量筛选NMNAT2激活剂的方法。
• Coordination of Thiosemicarbazones and Bis(thiosemicarbazones) to Bismuth(III) as a Strategy for the Design of Metal‐Based Antibacterial Agents
  作者：Josane A. Lessa、Débora C. Reis、Jeferson G. Da Silva、Lúcia T. Paradizzi、Nayane F. da Silva、Mariany de Fátima A. Carvalho、Sarah A. Siqueira、Heloisa Beraldo

  DOI：10.1002/cbdv.201100447

  日期：2012.9

  glyoxaldehyde bis(thiosemicarbazone) (H2Gy4DH) and its 4‐Et (H2Gy4Et) and 4‐Ph (H2Gy4Ph) derivatives. The complexes exhibited antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to BiIII proved to be an effective strategy to increase the antibacterial activity of the thiosemicarbazones and bis(thiosemicarbazones)

  配合物 [Bi(2Fo4Ph)Cl2] (1), [Bi(2Ac4Ph)Cl2] (2), [Bi(2Bz4Ph)Cl2] (3), [Bi(H2Gy3DH)Cl3] (4), [Bi(H2Gy4Et) (OH)2Cl] (5) 和 [Bi(H2Gy4Ph)Cl3] (6) 是用吡啶-2-甲醛 4-苯基缩氨基硫 (H2Fo4Ph)、1-(吡啶-2-基)乙酮 4-苯基缩氨基硫 (H2Ac4Ph) 制备的)、苯基(吡啶-2-基)甲酮4-苯基氨基硫脲(H2Bz4Ph)，以及乙醛双(氨基硫脲)(H2Gy4DH)及其4-Et(H2Gy4Et)和4-Ph(H2Gy4Ph)衍生物。该复合物对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和铜绿假单胞菌具有抗菌活性。事实证明，与 BiIII 的配合是提高缩氨基硫脲和双（缩氨基硫脲）抗菌活性的有效策略。
• 907. Heterocyclic systems related to pyrrocoline. Part II. The preparation of polyazaindenes by dehydrogenative cyclisations
  作者：J. D. Bower、G. R. Ramage

  DOI：10.1039/jr9570004506

  日期：——