(Z)-2-(4-oxo-5-(4-(pyrrolidin-1-yl)benzylidene)-2-thioxothiazolidin-3-yl)acetic acid | 313479-19-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (Z)-2-(4-oxo-5-(4-(pyrrolidin-1-yl)benzylidene)-2-thioxothiazolidin-3-yl)acetic acid
• 英文别名: 2-[(5Z)-4-oxo-5-[(4-pyrrolidin-1-ylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
• CAS: 313479-19-5
• 化学式: C₁₆H₁₆N₂O₃S₂
• 分子量: 348.447
• InChiKey: IEXBNGPRLUBIBP-LCYFTJDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(1-吡咯啉基)苯甲醛 、 3-羧甲基绕丹宁 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 7.0h， 生成 (Z)-2-(4-oxo-5-(4-(pyrrolidin-1-yl)benzylidene)-2-thioxothiazolidin-3-yl)acetic acid
  参考文献：
  名称：

  Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains

  摘要：

  There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer's diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50 = 19 nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100 nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72 h post fertilization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.039

文献信息

• RHODANINE DERIVATIVES FOR USE IN A METHOD OF INHIBITING AMYLOID PROTEIN AGGREGATION AND IMAGING AMYLOID DEPOSITS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1192143A1

  公开（公告）日：2002-04-03
• [EN] RHODANINE DERIVATIVES FOR USE IN A METHOD OF INHIBITING AMYLOID PROTEIN AGGREGATION AND IMAGING AMYLOID DEPOSITS<br/>[FR] DERIVES DE RHODANINE UTILISES DANS UN PROCEDE D'INHIBITION DE L'AGREGATION DE PROTEINES AMYLOIDES ET DE FORMATION D'IMAGES DE DEPOTS AMYLOIDES
  申请人：WARNER LAMBERT CO

  公开号：WO2000076987A1

  公开（公告）日：2000-12-21

  The present invention provides a method of treating Alzheimer's disease using a compound of Formula (I). Also provided is a method of inhibiting the aggregation of amyloid proteins using a compound of Formula (I) and a method of imaging amyloid deposits using compounds of Formula (I).
• Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer’s disease brains
  作者：Upendra Rao Anumala、Jiamin Gu、Fabio Lo Monte、Thomas Kramer、Roland Heyny-von Haußen、Jana Hölzer、Valerie Goetschy-Meyer、Christian Schön、Gerhard Mall、Ingrid Hilger、Christian Czech、Jochen Herms、Boris Schmidt

  DOI：10.1016/j.bmc.2013.06.039

  日期：2013.9

  There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer's diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50 = 19 nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100 nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72 h post fertilization. (C) 2013 Elsevier Ltd. All rights reserved.