5-(4-chlorobenzylidene)thiazolidine-2,4-dione potassium salt | 71995-35-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 5-(4-chlorobenzylidene)thiazolidine-2,4-dione potassium salt
• 英文别名: potassium;5-[(4-chlorophenyl)methylidene]-4-oxo-1,3-thiazol-2-olate
• CAS: 71995-35-2
• 化学式: C₁₀H₅ClNO₂S*K
• 分子量: 277.772
• InChiKey: ITJMKAOGWYRXDP-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.45
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-chlorobenzylidene)thiazolidine-2,4-dione potassium salt 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-(4-chlorophenyl)-1H-pyrazol-3-ol
  参考文献：
  名称：

  Omar, M. T.; Habashy, M. M.; Youssef, A. M., Journal fur praktische Chemie (Leipzig 1954), 1989, vol. 331, # 3, p. 393 - 398

  摘要：

  DOI：
• 作为产物：
  描述：

  5-(4-chloro-benzylidene)-thiazolidine-2,4-dione 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以70.66%的产率得到5-(4-chlorobenzylidene)thiazolidine-2,4-dione potassium salt
  参考文献：
  名称：

  Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells

  摘要：

  Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; their inhibition provides a strategy to disrupt tumor metabolism selectively, leading to antitumor effects. Here, novel thiazolidinedione (TZD) derivatives were designed, synthesized, characterized, and evaluated for their GLUT1, GLUT4, and GLUT5 inhibitory potential, followed by in-vitro cytotoxicity determination in leukemic cell lines. Compounds G5, G16, and G17 inhibited GLUT1, with IC50, values of 5.4 +/- 1.3, 26.6 +/- 1.8, and 12.6 +/- 1.2 mu M, respectively. G17 was specific for GLUT1, G16 inhibited GLUT4 (IC50 = 21.6 +/- 4.5 mu M) comparably but did not affect GLUT5. The most active compound, G5, inhibited all three GLUT types, with GLUT4 IC50 = 9.5 +/- 2.8 mu M, and GLUT5 IC50 = 34.5 +/- 2.4 mu M. Docking G5, G16, and G17 to the inward- and outward-facing structural models of GLUT1 predicted ligand binding affinities consistent with the kinetic inhibition data and implicated E380 and W388 of GLUT1 vs. their substitutions in GLUT5 (A388 and A396, respectively) in inhibitor preference for GLUT1. G5 inhibited the proliferation of leukemia CEM cells at low micromolar range (IC50 = 13.4 mu M) while being safer for normal blood cells. Investigation of CEM cell cycle progression after treatment with G5 showed that cells accumulated in the G2/M phase. Flow cytometric apoptosis studies revealed that compound G5 induced both early and late-stage apoptosis in CEM cells.

  DOI：

  10.1016/j.ejps.2020.105512

文献信息

• Design, synthesis, docking, ADMET profile, and anticancer evaluations of novel thiazolidine‐2,4‐dione derivatives as VEGFR‐2 inhibitors
  作者：Khaled El‐Adl、Helmy Sakr、Sanadelaslam S. A. El‐Hddad、Abdel‐Ghany A. El‐Helby、Mohamed Nasser、Hamada S. Abulkhair

  DOI：10.1002/ardp.202000491

  日期：2021.7

  one to the cytotoxic effect of the new derivatives. In particular, compounds 18, 11, and 10 were found to be the most potent derivatives among all the tested compounds against the HepG2, HCT-116, and MCF-7 cancer cell lines, with IC50 values ranging from 38.76 to 53.99 µM. The most active antiproliferative derivatives (7–14 and 15–19) were subjected to further biological studies to evaluate their inhibitory

  针对 HepG2、HCT-116 和 MCF-7 细胞评估了新型噻唑烷-2,4-二酮的抗癌活性。在测试的癌细胞系中，HCT-116 是对新衍生物的细胞毒性作用最敏感的细胞系。特别是化合物18，11，和10被认为是对抗的HepG2，HCT-116的所有测试的化合物中最有效的衍生物，和MCF-7癌细胞系，用IC 50个值范围从38.76至53.99微米。最活跃的抗增殖衍生物（7 – 14和15 – 19) 进行了进一步的生物学研究，以评估它们对 VEGFR-2 的抑制潜力。测试的化合物显示出良好到中等的抑制活性，IC 50值范围为 0.26 至 0.72 µM。其中，化合物18、11和10在 0.26–0.29 µM 范围内的IC 50值下有效抑制 VEGFR-2，几乎是索拉非尼 IC 50 的三倍值 (0.10 µM)。尽管我们的衍生物显示出低于参考药物的活性，但它们可用作未来设计、优化、适
• Solid–liquid phase equilibrium and thermodynamic analysis of novel thiazolidine-2,4-dione derivative in different solvents
  作者：Svetlana V. Blokhina、Angelica V. Sharapova、Marina V. Ol'khovich、Igor B. Levshin、German L. Perlovich

  DOI：10.1016/j.molliq.2020.115273

  日期：2021.3

  agent. Its melting enthalpy and melting point temperature were measured to be 44.4 kJ∙mol−1 and 433.9 K, respectively. The solubility of the compound studied was determined in pharmaceutically and industrially relevant organic solvents within the temperature range of 293.15–313.15 К. The solubility was found to increase in the systems with the following solvents: hexane, buffer рН 7.4, buffer рН 2.0, 1-octanol

  合成了新型（5Z）-3-（3-（4-乙酰基哌嗪-1-基）-2-羟丙基）-5-（4-氯亚苄基）噻唑烷-2,4-二酮作为有效的抗菌剂。测得其熔化焓和熔点温度为44.4 kJ∙mol -1和433.9K。在293.15–313.15К温度范围内，确定所研究化合物在药物和工业相关有机溶剂中的溶解度。发现在使用以下溶剂的系统中，溶解度增加：己烷，缓冲液7.4，缓冲液2.0、1-辛醇，1-丙醇，乙醇和甲醇。通过改进的Apelblat方程，两个后缀的Margules和Wilson模型将化合物的溶解度值关联起来，具有很好的一致性。计算了该化合物在每种溶剂中无限稀释时的活度系数和过量的热力学函数。使用汉森溶解度参数描述了化合物的分散，极性和氢相互作用的能力。化合物在1-辛醇/缓冲液（pH 2.0和7）中的分布系数与温度的关系。4）确定了两相系统。分布过程的特征是热力学上有利，受内生和熵驱动。
• Mechanistic Insights into Binding of Ligands with Thiazolidinedione Warhead to Human Histone Deacetylase 4
  作者：Markus Schweipert、Niklas Jänsch、Neha Upadhyay、Kalpana Tilekar、Ewelina Wozny、Sidra Basheer、Eva Wurster、Marlene Müller、Ramaa C S、Franz-Josef Meyer-Almes

  DOI：10.3390/ph14101032

  日期：——

  kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step

  最近，我们报道了非异羟肟酸噻唑烷二酮 (TZD) 类似物能够抑制人类脱乙酰酶 4 (HDAC4)。本研究旨在剖析 HDAC4 对 TZD 配体分子识别的分子决定因素和动力学。为此，将 225 种类似物的结构活性关系分析与对各种 HDAC4 突变变体的酶和结合动力学的综合研究相结合。通过对接HDAC4的两个主要构象，使实验数据合理化。TZD 配体是竞争性抑制剂，通过涉及主要分子识别和诱导拟合的两步机制结合。24 g 的停留时间为 (34 ± 3) min，因此远大于典型的 pan-HDAC 抑制剂 SAHA ((5 ± 2) min)。重要的，
• Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners
  作者：Igor B. Levshin、Alexander Y. Simonov、Sergey N. Lavrenov、Alexey A. Panov、Natalia E. Grammatikova、Alexander A. Alexandrov、Eslam S. M. O. Ghazy、Nikita A. Savin、Peter V. Gorelkin、Alexander S. Erofeev、Vladimir I. Polshakov

  DOI：10.3390/ph15050563

  日期：——

  Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in

  Mycosidine (3,5-取代的 thiazolidine-2,4-diones) 的新型衍生物是通过 Knoevenagel 缩合和噻唑烷与氯甲酸酯或卤代乙酸酯的反应合成的。此外，5-亚芳基-2,4-噻唑烷二酮及其在 5-亚苄基部分中含有卤素和羟基或二（苄氧基）取代基的 2-硫代类似物进行体外抗真菌活性测试。一些合成的化合物表现出很高的抗真菌活性，包括抑菌和杀真菌，并导致念珠菌的形态发生变化酵母细胞壁。基于在突变体中使用有限的蛋白质组学筛选和毒性分析，我们表明蕈碱活性与葡萄糖转运有关。这表明这种一流的抗真菌药物具有新的作用机制，值得进一步研究。
• Synthesis and Biological Evaluation of a Series of New Hybrid Amide Derivatives of Triazole and Thiazolidine-2,4-dione
  作者：Igor B. Levshin、Alexander Yu. Simonov、Alexey A. Panov、Natalia E. Grammatikova、Alexander I. Alexandrov、Eslam S. M. O. Ghazy、Vasiliy A. Ivlev、Michael O. Agaphonov、Alexey B. Mantsyzov、Vladimir I. Polshakov

  DOI：10.3390/ph17060723

  日期：——

  A series of hybrid compounds with triazole and thiazolidine nuclei connected by a linker has been synthesized and extensively studied. Various synthetic methods for the target compounds have been tested. A microbiological assessment of the obtained compounds was carried out on strains of pathogenic fungi C. albicans, C. non-albicans, multidrug-resistant C. auris, Rhizopus arrhizus, Aspergillus spp

  一系列具有通过连接体连接的三唑和噻唑烷核的杂化化合物已被合成并进行了广泛的研究。已经测试了目标化合物的各种合成方法。对所获得的化合物进行了病原真菌白色念珠菌、非白色念珠菌、多重耐药念珠菌、根霉、曲霉属菌株的微生物学评估。以及一些皮肤癣菌和其他酵母菌。目标化合物的最低 MIC 值在 0.003 µg/mL 至 0.5 µg/mL 之间，因此这些化合物不比商业唑类药物差或好几倍。酰基哌嗪接头的长度对抗真菌活性的影响有限。一些生物等排类似物在微生物分析中进行了测试，但结果证明其活性弱于先导物质。噻唑烷片段中具有对氯亚苄基取代基的化合物表现出最高的活性。分子模型用于预测合成分子的结合模式并合理化实验观察到的 SAR。与伏立康唑相比，前导化合物在抑制白色念珠菌酵母细胞形成芽管方面的效果高出两倍。观察到吡咯类药物外排泵 Pdr5 水平增加，但增加幅度低于唑类引起的水平。研究结果可用于进一步开发更强大、更安全的抗真菌药物。