3-[(4-氟苯基)甲基]-1,3-噻唑烷-2,4-二酮 | 137660-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 3-[(4-氟苯基)甲基]-1,3-噻唑烷-2,4-二酮
• 英文名称: 3-(4-fluorobenzyl)thiazolidine-2,4-dione
• 英文别名: 2,4-Thiazolidinedione, 3-[(4-fluorophenyl)methyl]-；3-[(4-fluorophenyl)methyl]-1,3-thiazolidine-2,4-dione
• CAS: 137660-67-4
• 化学式: C₁₀H₈FNO₂S
• mdl: MFCD03032210
• 分子量: 225.243
• InChiKey: GTAZAXSMXJLHEP-UHFFFAOYSA-N

物化性质

• 熔点：
  83 °C(Solv: ethanol (64-17-5))
• 沸点：
  352.1±44.0 °C(Predicted)
• 密度：
  1.455±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(4-氟苯基)甲基]-1,3-噻唑烷-2,4-二酮 在 哌啶 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.25h， 生成 triisopropylsilyl-(Z)-4-((4-((3-(4-fluorobenzyl)-2,4-dioxothiazolidin-5-ylidene)methyl)-2-(2-(2-hydroxyethoxy)ethoxy)phenoxy)methyl)benzoate
  参考文献：
  名称：

  新型自分泌抑制因子-Icodextrin缀合物的合成与活性

  摘要：

  Autotaxin是一种细胞外磷脂酶D，可催化溶血磷脂酰胆碱（LPC）的水解以产生生物活性脂质溶血磷脂酸（LPA）。自分泌运动因子已经牵涉到许多与癌症有关的病理过程中。腹膜内施用自分泌运动抑制剂可能使卵巢癌患者受益；然而，已知低分子量化合物可从腹膜腔中迅速清除。艾考曲宁是一种已经在临床上使用的聚合物，因为它可以从腹膜腔中缓慢清除。在本文中，我们报道了自分泌紫杉醇抑制剂HA155与艾考糊精的缀合。结合物抑制自分泌运动蛋白活性（IC 50 = 0.86±0.13μgmL –1）并减少细胞迁移。抑制剂的缀合增加了其溶解度，降低了其膜通透性，并改善了其在小鼠中的腹膜内滞留性。这些观察结果证明了艾考糊精作为一种共价结合的药物递送平台的首次应用，具有潜在的治疗卵巢癌的潜力。

  DOI：

  10.1021/acs.jmedchem.8b00935
• 作为产物：
  描述：

  1,3-thiazolidine-2,4-dione potassium salt 、 alkaline earth salt of/the/ methylsulfuric acid 以 N,N-二甲基甲酰胺 为溶剂， 以93%的产率得到3-[(4-氟苯基)甲基]-1,3-噻唑烷-2,4-二酮
  参考文献：
  名称：

  Thiazolidinone–Peptide Hybrids as Dengue Virus Protease Inhibitors with Antiviral Activity in Cell Culture

  摘要：

  The protease of dengue virus is a promising target for antiviral drug discovery. We here report a new generation of peptide hybrid inhibitors of dengue protease that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The compounds were extensively characterized with respect to inhibition of various proteases, inhibition mechanisms, membrane permeability, antiviral activity, and cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide hybrids) has a significant effect on these properties and activities. The most promising in vitro affinities were observed for thiazolidinedione-based peptide hybrids containing hydrophobic groups with K-i values between 1.5 and 1.8 mu M and competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with hydrophobic substituents have, in correlation with their membrane permeability, a more pronounced antiviral activity in cell culture than the thiazolidinediones.

  DOI：

  10.1021/jm400828u

文献信息

• Free radical scavenging activity of novel thiazolidine-2,4-dione derivatives
  作者：Paweł Berczyński、Irena Kruk、Teresa Piechowska、Meltem Ceylan-Unlusoy、Oya Bozdağ-Dündar、Hassan Y. Aboul-Enein

  DOI：10.1002/bio.2454

  日期：2013.11

  Free radical activity towards superoxide anion radical (), hydroxyl radical (HO•) and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•) of a series of novel thiazolidine‐2,4‐dione derivatives (TSs) was examined using chemiluminescence, electron paramagnetic resonance (EPR) and EPR spin trapping techniques. 5,5‐Dimethyl‐1‐pyrroline‐N‐oxide (DMPO) was applied as the spin trap. Superoxide radical was produced in

  使用化学发光法检测了一系列新型噻唑烷-2,4-二酮衍生物（TSs）对超氧阴离子自由基（），羟基自由基（HO •）和2,2-二苯基-1-吡啶并肼基（DPPH •）的自由基活性，电子顺磁共振（EPR）和EPR自旋俘获技术。5,5-二甲基-1-吡咯啉-N-氧化物（DMPO）被用作自旋阱。溶于二甲亚砜的超氧化钾/ 18-冠-6醚中产生超氧化物自由基。在Fenton反应中生成了羟基自由基（Fe（II）+ H 2 O 2。发现TSs对DPPH自由基显示出轻微的清除作用（在2.5 mmol / L的浓度下减少了15-38％）和较高的清除作用（41-88％）。所测试的化合物显示出对HO •依赖性DMPO-OH自旋加合物形成的抑制作用（在2.5 mmol / L的浓度下，EPR信号的幅度下降20％至76％。我们的发现提出了对自由基具有较高反应性的新型化合物。版权所有©2012 John Wiley＆Sons，Ltd
• Synthesis and hypoglycemic activity of some substituted flavonyl thiazolidinedione derivatives—fifth communication: flavonyl benzyl substituted 2,4-thiazolidinediones
  作者：Meral Tunçbilek、Oya Bozdağ-Dündar、Gülgün Ayhan-Kılcıgil、Meltem Ceylan、Abdül Waheed、Eugen J Verspohl、Rahmiye Ertan

  DOI：10.1016/s0014-827x(02)01241-7

  日期：2003.1

  A new series of 3-benzyl(p-substituted benzyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones (8a-e) were synthesized. These products were prepared by Knoevenagel reaction from 3'-flavone carboxaldehyde and 3-substituted 2,4-thiazolidinediones. In vitro insulinotropic activity was determined for compounds 6a-e, 7a-e, 8b and 8c.

  一系列新的3-苄基（对取代苄基）-5- [3'-（4H-4-氧代-1-苯并吡喃-2-基）-亚苄基] -2,4-噻唑烷二酮（8a-e）为合成的。这些产物是通过Knoevenagel反应从3'-黄酮羧醛和3-取代的2,4-噻唑烷二酮制备的。测定化合物6a-e，7a-e，8b和8c的体外促胰岛素活性。
• Novel Furochromone Derivatives: Synthesis and Anticancer Activity Studies
  作者：Senem Demir、Cigdem Özen、Meltem Ceylan‐Ünlüsoy、Mehmet Öztürk、Oya Bozdağ‐Dündar

  DOI：10.1002/jhet.3508

  日期：2019.4

  Medicinal plant extracts have been used for medical purposes throughout human history. In this study, khellin, having furochromone structure, which is obtained from a well‐known traditional medicinal plant, was selected. A series of furochromonyl compounds (K1–K14) were synthesized for their anticancer activities. Furochromonyl compounds (K1–K14) were synthesized by Knoevenagel reaction of substituted 2

  药用植物提取物已在整个人类历史上用于医学目的。在这项研究中，选择了具有呋喃苯醌结构的凯勒琳，其是从著名的传统药用植物中获得的。合成了一系列呋喃苯甲酰基化合物（K1 - K14）以具有抗癌活性。呋喃苯甲酰基化合物（K1 - K14）是通过取代的2,4-噻唑烷二酮（Ia - j）/若丹宁（Ik - n）与Khellin-2-羧醛（V）的Knoevenagel反应合成的），并在22种癌细胞系中研究了它们的细胞毒性，这些癌细胞系来自肝脏，乳房，结肠和子宫颈等组织。第一步，将两种肝细胞癌细胞系Huh7和PLC / PRF / 5（Alexander细胞）分别用10μM的化合物处理72小时，然后进行磺基罗丹明B检测以分析其抗生长活性。乙基2-（5-（（（4,9-二甲氧基-5-氧代-5 H-呋喃[3,2 - g ]铬n-7-基）亚甲基）-4-氧代-2-硫代噻唑并恶唑烷-3-基）乙酸盐（K11）被发现是初
• Synthesis and antimicrobial activity of novel 5-[(1H-indol-3-yl)methylene]thiazolidine-2,4-dione–[1,2,3]triazole hybrids
  作者：L. Kamala、B. S. Veena、P. V. Anantha Lakshmi、P. Vasantha、E. Sujatha

  DOI：10.1134/s107036321702027x

  日期：2017.2

  ]thiazolidine-2,4-dione–[1,2,3]triazole hybrid derivatives were synthesized by click chemistry reaction and screened for antimicrobial activity against Gram positive and Gram negative bacteria and fungal species. All synthesized compounds were characterized by 1H and 13C NMR, IR and MS spectra. Antibacterial study indicated that several products demonstrated high activity and some products were determined

  通过点击化学反应合成了5-[（1 H-吲哚-3-基）亚甲基]噻唑烷-2,4-二酮-[1,2,3]三唑杂化衍生物，并筛选了对革兰氏阳性和革兰氏阴性的抗菌活性细菌和真菌种类。所有合成的化合物均通过1 H和13 C NMR，IR和MS光谱表征。抗菌研究表明，几种产品显示出高活性，某些产品被确定为潜在的抗真菌活性剂。
• Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation
  作者：Harald M. H. G. Albers、Anping Dong、Laurens A. van Meeteren、David A. Egan、Manjula Sunkara、Erica W. van Tilburg、Karianne Schuurman、Olaf van Tellingen、Andrew J. Morris、Susan S. Smyth、Wouter H. Moolenaar、Huib Ovaa

  DOI：10.1073/pnas.1001529107

  日期：2010.4.20

  Autotaxin (ATX) is a secreted nucleotide pyrophosphatase/phosphodiesterase that functions as a lysophospholipase D to produce the lipid mediator lysophosphatidic acid (LPA), a mitogen, chemoattractant, and survival factor for many cell types. The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation, fibrotic diseases and tumor progression, making this system an attractive target for therapy. However, potent and selective nonlipid inhibitors of ATX are currently not available. By screening a chemical library, we have identified thiazolidinediones that selectively inhibit ATX-mediated LPA production both in vitro and in vivo. Inhibitor potency was approximately 100-fold increased (IC ₅₀  ∼ 30 nM) after the incorporation of a boronic acid moiety, designed to target the active-site threonine (T210) in ATX. Intravenous injection of this inhibitor into mice resulted in a surprisingly rapid decrease in plasma LPA levels, indicating that turnover of LPA in the circulation is much more dynamic than previously appreciated. Thus, boronic acid-based small molecules hold promise as candidate drugs to target ATX.

  Autotaxin（ATX）是一种分泌的核苷酸焦磷酸酶/磷酸二酯酶，作为一种溶酶磷脂酶D，产生脂质介质溶酶磷脂酸（LPA），是许多细胞类型的有丝分裂原、趋化因子和生存因子。ATX-LPA信号通路已被认为在血管生成、慢性炎症、纤维化疾病和肿瘤进展中起作用，使得这个系统成为治疗的有吸引力的目标。然而，目前没有有效和选择性的非脂类ATX抑制剂。通过筛选化学库，我们已经确定了噻唑烷二酮，这些噻唑烷二酮能够选择性地抑制体外和体内ATX介导的LPA产生。抑制剂的效力在加入硼酸基团后大约提高了100倍（IC50约为30 nM），设计该基团是为了靶向ATX中的活性位点苏氨酸（T210）。将该抑制剂静脉注射到小鼠体内，导致血浆LPA水平出现惊人的快速下降，表明循环中LPA的周转比以前估计的要动态得多。因此，基于硼酸的小分子化合物有望成为用于靶向ATX的候选药物。