[(Z)-2-(5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)]acetic acid | 1208535-12-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(Z)-2-(5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)]acetic acid
• 英文别名: 2-[(5Z)-5-[(3,4-dihydroxyphenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
• CAS: 1208535-12-9
• 化学式: C₁₂H₉NO₅S₂
• 分子量: 311.339
• InChiKey: MNPZQUQRMCXSTL-WTKPLQERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-[5-(3,4-dimethoxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acid 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以76%的产率得到[(Z)-2-(5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl)]acetic acid
  参考文献：
  名称：

  Catechol–rhodanine derivatives: Specific and promiscuous inhibitors of Escherichia coli deoxyxylulose phosphate reductoisomerase (DXR)

  摘要：

  To develop more effective inhibitors than fosmidomycin, a natural compound which inhibits the deoxyxylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the MEP pathway, we designed molecules possessing on the one hand a catechol that is able to chelate the magnesium dication and on the other hand a group able to occupy the NADPH recognition site. Catechol-rhodanine derivatives (1-6) were synthesized and their potential inhibition was tested on the DXR of Escherichia coli. For the inhibitors 1 and 2, the presence of detergent in the enzymatic assays led to a dramatic decrease of the inhibition suggesting, that these compounds are rather promiscuous inhibitors. The compounds 4 and 5 kept their inhibition capacity in the presence of Triton X100 and could be considered as specific inhibitors of DXR. Compound 4 showed antimicrobial activity against Escherichia coli. The only partial protection of NADPH against the inhibition suggested that the catechol-rhodanine derivatives did not settle in the coenzyme binding site. This paper points out the necessity to include a detergent in the DXR enzymatic assays to avoid false positive when putative hydrophobic inhibitors are tested and especially when the IC50, are in the micromolar range.

  DOI：

  10.1016/j.bmc.2014.05.004

文献信息

• 5-Benzylidenethiazolidin-4-ones as Multitarget Inhibitors of Bacterial Mur Ligases
  作者：Tihomir Tomašić、Nace Zidar、Andreja Kovač、Samo Turk、Mihael Simčič、Didier Blanot、Manica Müller-Premru、Metka Filipič、Simona Golič Grdadolnik、Anamarija Zega、Marko Anderluh、Stanislav Gobec、Danijel Kikelj、Lucija Peterlin Mašič

  DOI：10.1002/cmdc.200900449

  日期：2010.2.1

  Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series of hydroxy‐substituted 5‐benzylidenethiazolidin‐4‐ones were synthesized and tested as inhibitors of Mur ligases. The most potent compound 5 a was active against MurD–F with IC50 values between 2 and 6 μm

  Mur连接酶参与细菌肽聚糖生物合成的细胞内途径，并构成了诱人的药物靶标，尽管到目前为止尚未被充分利用。合成了一系列羟基取代的5-亚苄基硫唑烷丁-4-酮，并作为Mur连接酶的抑制剂进行了测试。最有效的化合物5a 具有抗MurD-F的活性，IC 50值在2至6μm之间，使其成为有希望的Mur连接酶的多靶点抑制剂。还研究了对不同菌株的抗菌活性，对蛋白激酶的抑制活性，5a 的致突变性和遗传毒性，并进行了动力学和NMR研究。
• <scp>L‐proline</scp>‐based <scp>DES</scp> in Knoevenagel synthesis of arylidene rhodanines, thiazolidine‐2,4‐diones, and barbituric derivatives
  作者：Stéphanie Hesse、Jasmine Hertzog、Sandrine Rup‐Jacques

  DOI：10.1002/jhet.4819

  日期：——

  compounds (VOC) are often still used during workup and isolation of products. Here, a zero-VOC strategy for Knoevenagel reaction is reported. (Hetero)aromatic aldehydes are successfully condensed with rhodanine, thiazolidine-2,4-dione TZD, or barbituric acid under mild conditions in an L-proline-based DES and pure compounds are obtained after hydrolysis without any purification. For the less reactive TZD

  低共熔溶剂（DES）是一种环境友好型溶剂，可以避免使用有毒有机溶剂，近年来得到了广泛的研究。然而，在产品的后处理和分离过程中仍然经常使用挥发性有机化合物 (VOC)。本文报道了 Knoevenagel 反应的零 VOC 策略。在温和条件下，（杂）芳香醛与绕丹宁、噻唑烷-2,4-二酮 TZD 或巴比妥酸在 L-脯氨酸基 DES 中成功缩合，水解后无需任何纯化即可获得纯化合物。对于反应性较低的 TZD，微波激活可以将反应时间从 24 小时缩短至仅 1 小时。
• Chemical Proteomic Assay for Optimizing Drug Binding to Target Proteins
  申请人：Sem Daniel S.

  公开号：US20100304998A1

  公开（公告）日：2010-12-02

  Disclosed herein are methods related to drug development. The methods typically include steps whereby an existing drug is modified to obtain a derivative form or whereby an analog of an existing drug is identified in order to obtain a new therapeutic agent that preferably has a higher efficacy and fewer side effects than the existing drug.
• Catechol–rhodanine derivatives: Specific and promiscuous inhibitors of Escherichia coli deoxyxylulose phosphate reductoisomerase (DXR)
  作者：Catherine Zinglé、Denis Tritsch、Catherine Grosdemange-Billiard、Michel Rohmer

  DOI：10.1016/j.bmc.2014.05.004

  日期：2014.7

  To develop more effective inhibitors than fosmidomycin, a natural compound which inhibits the deoxyxylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the MEP pathway, we designed molecules possessing on the one hand a catechol that is able to chelate the magnesium dication and on the other hand a group able to occupy the NADPH recognition site. Catechol-rhodanine derivatives (1-6) were synthesized and their potential inhibition was tested on the DXR of Escherichia coli. For the inhibitors 1 and 2, the presence of detergent in the enzymatic assays led to a dramatic decrease of the inhibition suggesting, that these compounds are rather promiscuous inhibitors. The compounds 4 and 5 kept their inhibition capacity in the presence of Triton X100 and could be considered as specific inhibitors of DXR. Compound 4 showed antimicrobial activity against Escherichia coli. The only partial protection of NADPH against the inhibition suggested that the catechol-rhodanine derivatives did not settle in the coenzyme binding site. This paper points out the necessity to include a detergent in the DXR enzymatic assays to avoid false positive when putative hydrophobic inhibitors are tested and especially when the IC50, are in the micromolar range.