1,1-Dioxo-3-[1-phenyl-meth-(Z)-ylidene]-1λ⁶-thiochroman-4-one | 91145-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 1,1-Dioxo-3-[1-phenyl-meth-(Z)-ylidene]-1λ⁶-thiochroman-4-one
• 英文别名: 3-Benzylidene-1,1-dioxothiochromen-4-one；3-benzylidene-1,1-dioxothiochromen-4-one
• CAS: 91145-25-4
• 化学式: C₁₆H₁₂O₃S
• 分子量: 284.335
• InChiKey: LTEHPJVQXONERT-UHFFFAOYSA-N

物化性质

• 熔点：
  176 °C(Solv: ethanol (64-17-5))
• 沸点：
  538.7±50.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯甲醛 、 1,1-二氧代-1lambda*6*-硫代色满-4-酮 生成 1,1-Dioxo-3-[1-phenyl-meth-(Z)-ylidene]-1λ⁶-thiochroman-4-one
  参考文献：
  名称：

  Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice

  摘要：

  Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine playing crucial role in immunity. MIF exerts a unique tautomerase enzymatic activity that has relevance concerning its multiple functions and its small molecule inhibitors have been proven to block its pro-inflammatory effects. Here we demonstrate that some of the E-2-arylmethylene-1-tetralones and their heteroanalogues efficiently bind to MIF's active site and inhibit MIF tautomeric (enolase, ketolase activity) functions. A small set of the synthesised derivatives, namely compounds (4), (23), (24), (26) and (32), reduced inflammatory macrophage activation. Two of the selected compounds (24) and (26), however, markedly inhibited ROS and nitrite production, NF-κB activation, TNF-α, IL-6 and CCL-2 cytokine expression. Pre-treatment of mice with compound (24) exaggerated the hypothermic response to high dose of bacterial endotoxin. Our experiments suggest that tetralones and their derivatives inhibit MIF's tautomeric functions and regulate macrophage activation and thermal changes in severe forms of systemic inflammation.

  DOI：

  10.1080/14756366.2021.1916010

文献信息

• Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice
  作者：János Garai、Marcell Krekó、László Őrfi、Péter Balázs Jakus、Zoltán Rumbus、Patrik Kéringer、András Garami、Eszter Vámos、Dominika Kovács、Viola Bagóné Vántus、Balázs Radnai、Tamás Lóránd

  DOI：10.1080/14756366.2021.1916010

  日期：2021.1.1

  Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine playing crucial role in immunity. MIF exerts a unique tautomerase enzymatic activity that has relevance concerning its multiple functions and its small molecule inhibitors have been proven to block its pro-inflammatory effects. Here we demonstrate that some of the E-2-arylmethylene-1-tetralones and their heteroanalogues efficiently bind to MIF's active site and inhibit MIF tautomeric (enolase, ketolase activity) functions. A small set of the synthesised derivatives, namely compounds (4), (23), (24), (26) and (32), reduced inflammatory macrophage activation. Two of the selected compounds (24) and (26), however, markedly inhibited ROS and nitrite production, NF-κB activation, TNF-α, IL-6 and CCL-2 cytokine expression. Pre-treatment of mice with compound (24) exaggerated the hypothermic response to high dose of bacterial endotoxin. Our experiments suggest that tetralones and their derivatives inhibit MIF's tautomeric functions and regulate macrophage activation and thermal changes in severe forms of systemic inflammation.