(E)-4′-fluoroacetophenone thiosemicarbazone

• 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: (E)-4′-fluoroacetophenone thiosemicarbazone
• 英文别名: [(E)-1-(4-fluorophenyl)ethylideneamino]thiourea
• 化学式: C₉H₁₀FN₃S
• 分子量: 211.263
• InChiKey: JBOMIBNEKCISGH-WUXMJOGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4′-fluoroacetophenone thiosemicarbazone 在 盐酸羟胺 、 sodium hydride 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 14.08h， 生成 (E)-N-hydroxy-6-(2-(1-(4-fluorophenyl)ethylidene)hydrazin-1-ylthiocarbonylamino)hexanamide
  参考文献：
  名称：

  Discovery of thiosemicarbazone-containing compounds with potent anti-proliferation activity against drug-resistant K562/A02 cells

  摘要：

  P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle to successful chemotherapy for leukemia. In this study, a series of thiosemicarbazone-containing compounds (4a-b, 7a-q) were synthesized. Biological evaluation showed that the most active compound 7e displayed potent anti-leukemia activity against P-gp overexpressing drug-resistant K562/A02 cells, with an IC₅₀ value of 0.44 μM. Notably, compound 7e exhibited a selective killing effect on K562/A02 cells by dose-dependently increasing the intracellular levels of reactive oxygen species (ROS), thus exerting a potential collateral sensitivity (CS)-promoting effect in vitro. Moreover, compound 7e could inhibit HDAC1 and HDAC6, and induce the apoptosis of K562/A02 cells by increasing the expression of Bax, decreasing Bcl-2 protein level, and promoting the cleavage of caspase-3 and PARP, respectively. Overall, 7e may be a potential anti-cancer agent against drug-resistant myelogenous leukemia.

  DOI：

  10.1016/j.bmcl.2020.127638
• 作为产物：
  描述：

  4-氟苯乙酮 、 氨基硫脲 以 乙醇 为溶剂， 反应 8.0h， 以90%的产率得到(E)-4′-fluoroacetophenone thiosemicarbazone
  参考文献：
  名称：

  卤代芳香族硫半脲类作为酪氨酸酶和黑色素生成的有效抑制剂。

  摘要：

  已经合成了一组21个卤代硫代半氨基甲酮（TSC），并研究了其对蘑菇酪氨酸酶活性双酚酶的抑制特性以及它们在B16F10小鼠黑素瘤细胞系中抑制黑素生成的能力。还进行了与酶活性位点的分子对接，以研究酶-抑制剂相互作用的性质。获得的结果使我们能够进行SAR分析。TSC 6、12和21表现出最强的抑制特性，IC50分别为0.5、0.9和0.8 µM。他们揭示了酪氨酸酶抑制作用的可逆性和竞争性方式。根据SAR分析，在所研究的化合物中，硫代半氨基甲酮的对位取代的苯乙酮衍生物对该酶具有最高的亲和力。B16F10细胞中黑色素的产生被所有研究的化合物以微摩尔水平抑制。建议的抑制机理是基于硫代半氨基甲酮的硫脲部分的硫原子与酶活性位点中的铜离子之间的相互作用。这些结果可能有助于寻找可用于化妆品和食品工业的新型黑色素生成抑制剂。

  DOI：

  10.1016/j.bioorg.2019.103419

文献信息

• Structural improvement of new thiazolidinones compounds with antinociceptive activity in experimental chemotherapy-induced painful neuropathy
  作者：Diogo Rodrigo Magalhaes Moreira、Dourivaldo Silva Santos、Renan Fernandes do Espírito Santo、Flávia Evangelista dos Santos、Gevanio Bezerra de Oliveira Filho、Ana Cristina Lima Leite、Milena Botelho Pereira Soares、Cristiane Flora Villarreal

  DOI：10.1111/cbdd.12951

  日期：2017.8

  cure chemotherapy-induced neuropathy. In the present study, we describe the structural design, synthesis, chemical and pharmacological characterization of 15 thiazolidinones, a class of potential analgesic compounds. The synthesis of new thiazolidinones was achieved by using the thiazolidinone heterocyclic as main structural pharmacophoric group and varying the substituents attached to the phenyl near

  化学疗法诱发的神经病是癌症化疗导致的致残性疼痛症状。到目前为止，尚无可用于治疗化学疗法诱发的神经病的药物。在本研究中，我们描述了15种噻唑烷酮（一种潜在的止痛化合物）的结构设计，合成，化学和药理学表征。通过使用噻唑烷酮杂环作为主要结构药效基团并改变连接至亚氨基键附近的苯基的取代基，可以合成新的噻唑烷酮。使用von Frey，rota-rod和开放视野试验，在奥沙利铂诱导的神经性疼痛的小鼠模型中研究了该化合物的镇痛潜力。除化合物14外，这些噻唑烷酮类具有镇痛特性，而不会引起运动障碍。噻唑烷酮12 图15和图16显示了剂量依赖性的抗伤害感受作用，与加巴喷丁（一种用于神经性疼痛的金标准药物）相比，具有相似的功效和增强的功效。此外，16的抗伤害感受活性比加巴喷丁持续时间更长。噻唑烷酮的抗伤害感受作用被PPARγ拮抗剂GW9662阻止。主要的抗伤害感受性化合物表现出Lipinski指数阳性，预示其口
• The preparation of N-(1<i>H</i>-pyrazol-3-yl)arylamides and 1<i>H</i>-pyrazol-3-amines from polylithiated C(α),<i>N</i>-thiosemicarbazones and C(α),<i>N</i>-semicarbazones
  作者：Charles F. Beam、Sharon E. Davis、Tracy L. Cordray、Kam W. Chan、Camille M. Kassis、Joanna G. Freeman Davis、G. Mark Latham、Tina S. Guion、Karen C. Hildebran、A. Cameron Church、Madlene U. Koller、Clyde R. Metz、William T. Pennington、Kevin L. Schey

  DOI：10.1002/jhet.5570340527

  日期：1997.9

  C(α),N-Thiosemicarbazones or C(α),N-semicarbazones were polylithiated with excess lithium diiso-propylamide, and the resulting cyclized intermediates were condensed with aromatic esters to afford N-(1H-pyrazol-3-yl)arylamides. The polylithiated intermediates were also quenched with aqueous acid to give 5-substituted, 1H-pyrazol-3-amines.

  Ç（α），Ñ -Thiosemicarbazones或Ç（α），Ñ -semicarbazones用过量的二异锂丙酰胺polylithiated，并将得到的环化的中间体用芳香酯缩合，得到ñ - （1 ħ吡唑-3-基）芳基酰胺。还用酸水溶液淬灭多聚的中间体，得到5-取代的1H-吡唑-3-胺。
• Thiadiazoline derivative
  申请人：Murakata Chikara

  公开号：US20060074113A1

  公开（公告）日：2006-04-06

  (wherein R 1 and R 4 are the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkenyl, or the like; R 5 represents a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, or the like; R 2 represents —C(═W)R 6 or the like; R 3 represents a hydrogen atom, —C(═W A )R 6A , or the like) Antitumor agents which comprises a thiadiazoline derivative represented by the aforementioned general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient are provided.

  提供了一种抗肿瘤剂，其中R1和R4相同或不同，每个代表氢原子，取代或未取代的低级烷基，取代或未取代的低级炔基，取代或未取代的低级烯基或类似物；R5代表取代或未取代的杂环基，取代或未取代的芳基或类似物；R2代表-C（═W）R6或类似物；R3代表氢原子，-C（═WA）R6A或类似物。该抗肿瘤剂包含由上述通式（I）表示的噻二唑啉衍生物或其药理学上可接受的盐作为活性成分。
• THIADIAZOLINE DERIVATIVE
  申请人：MURAKATA Chikara

  公开号：US20080207706A1

  公开（公告）日：2008-08-28

  (wherein R 1 and R 4 are the same or different and each represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkynyl, substituted or unsubstituted lower alkenyl, or the like; R 5 represents a substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, or the like; R 2 represents —C(═W)R 6 or the like; R 3 represents a hydrogen atom, —C(═W A )R 6A , or the like) Antitumor agents which comprises a thiadiazoline derivative represented by the aforementioned general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient are provided.

  提供了一种抗肿瘤剂，其包括由上述一般式（I）表示的噻二唑啉衍生物或其药学上可接受的盐作为活性成分，其中R1和R4相同或不同，每个代表氢原子，取代或未取代的低碳基，取代或未取代的低炔基，取代或未取代的低烯基或类似物; R5代表取代或未取代的杂环基，取代或未取代的芳基或类似物; R2代表-C（═W）R6或类似物; R3代表氢原子，-C（═WA）R6A或类似物。
• Mitotic kinesin inhibitor
  申请人：Murakata Chikara

  公开号：US20070155804A1

  公开（公告）日：2007-07-05

  A mitotic kinesin Eg5 inhibitor which comprises a thiadiazoline derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient: [wherein R 1 represents a hydrogen atom and the like, R 2 represents a hydrogen atom, —C(═W)R 6 (wherein W represents an oxygen atom or a sulfur atom, and R 6 represents substituted or unsubstituted lower alkyl and the like) and the like, R 3 represents —C(═Z)R 19 (wherein Z represents an oxygen atom or a sulfur atom, and R 19 represents substituted or unsubstituted lower alkyl and the like) and the like, R 4 represents substituted or unsubstituted lower alkyl and the like, and R 5 represents substituted or unsubstituted aryl and the like] and the like are provided.

  一种有丝分裂动力蛋白Eg5抑制剂，其包括由通式（I）表示的噻二唑衍生物或其药学上可接受的盐作为活性成分：[其中R1代表氢原子等，R2代表氢原子，-C（═W）R6（其中W代表氧原子或硫原子，R6代表取代或未取代的低级烷基等）等，R3代表-C（═Z）R19（其中Z代表氧原子或硫原子，R19代表取代或未取代的低级烷基等）等，R4代表取代或未取代的低级烷基等，R5代表取代或未取代的芳基等]等。