(Z)-2-(5-((10-octyl-10H-phenothiazin-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid | 1450722-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: (Z)-2-(5-((10-octyl-10H-phenothiazin-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid
• 英文别名: 2-[(5Z)-5-[(10-octylphenothiazin-3-yl)methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid
• CAS: 1450722-18-5
• 化学式: C₂₆H₂₈N₂O₃S₃
• 分子量: 512.718
• InChiKey: UUHCZXXCGIBPDD-KQWNVCNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  144
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-溴辛烷 在 sodium acetate 、 sodium hydride 、 三氯氧磷 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 (Z)-2-(5-((10-octyl-10H-phenothiazin-3-yl)methylene)-4-oxo-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

• 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.