N-(3,4-dihydroxyphenylethyl)-5-(1,2-dithiolan-3-yl)pentanamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二硫杂环戊烷
• 英文名称: N-(3,4-dihydroxyphenylethyl)-5-(1,2-dithiolan-3-yl)pentanamide
• 英文别名: N-(3,4-dihydroxyphenethyl)-5-(1,2-dithiolan-3-yl)pentanamide；HBU-199；N-[2-(3,4-dihydroxyphenyl)ethyl]-5-(1,2-dithiolan-3-yl)pentanamide；N-[2-(3,4-dihydroxyphenyl)ethyl]-5-(dithiolan-3-yl)pentanamide
• 化学式: C₁₆H₂₃NO₃S₂
• 分子量: 341.496
• InChiKey: LSCVFMCTEXGPFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3,4-dihydroxyphenylethyl)-5-(1,2-dithiolan-3-yl)pentanamide 、 乙酸酐 在 caesium carbonate 作用下， 以 二氯甲烷 为溶剂， 以68%的产率得到4-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)-1,2-phenylene diacetate
  参考文献：
  名称：

  A dopamine-alpha-lipoic acid hybridization compound and its acetylated form inhibit LPS-mediated inflammation

  摘要：

  In the present study, we synthesized and evaluated the anti-inflammatory effects of dopamine and alpha-lipoic acid (ALA) hybrid compounds, ALA-dopamine (HBU-199) and its acetylated derivative, ALA-acetyl dopamine (HBU-200), in BV2 microglia and RAW264.7 macrophage cells. HBU-199 and HBU-200 both significantly and dose dependently inhibited LPS-induced nitric oxide (NO) productions, NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 and interleukin-1 beta mRNA expressions and iNOS and COX-2 protein expressions. Furthermore, HBU-199 and HBU-200 protected RAW264.7 cells from activation induced cell death. However, at same concentrations, dopamine or ALA did not inhibit LPS-medialed production of inflammatory molecules and activation induced cell death. HBU-199 and HBU-200 inhibited LPS-induced inhibition of inhibitory kappa-B-alpha (I kappa B-alpha) phosphorylalion and nuclear factor kappa B (NF-kappa B) activation. Furthermore, LPS mediated DNA binding of p65 and p50 to the NF-kappa B binding site of the iNOS promoter was inhibited by HBU-199 and HBU-200, whereas dopamine and ALA did not inhibit LPS induced NF-kappa B activation and I kappa B-alpha phosphorylalion. Moreover, HBU-199 and HBU-200 suppressed LPS stimulated phosphorylalion of Akt. but not glycogen synthase kinase 3 beta. Overall, our data suggest that the ALA-dopamine hybrid compounds down-regulate inflammatory responses via inhibition of NE-kappa B and NF-kappa B-dependent gene expression, suggesting that it is a promising therapeutic agent for both systemic inflammatory diseases and inflammatory diseases of central nervous system. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2014.10.052
• 作为产物：
  描述：

  C₁₈H₂₇O₃NS₂ 在 BF₃*S(Me)2 作用下， 以 二氯甲烷 为溶剂， 以46%的产率得到N-(3,4-dihydroxyphenylethyl)-5-(1,2-dithiolan-3-yl)pentanamide
  参考文献：
  名称：

  Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity

  摘要：

  We designed and synthesized new analogues containing 1,2-dithiolane-3-alkyl and protected or free catechol moieties connected through heteroaromatic rings such as triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, tetrazole or thiazole in order to explore the influence of the bioisosteric replacement of the amide group on the neuroprotective activity of the lipoic acid/dopamine conjugate. Evaluation of the activity of the new compounds, using glutamate-challenged hippocampal HT22 cells, showed that incorporation of heteroaromatic rings in the alkyl-1,2-dithiolane moieties in conjunction with another antioxidant, in this case catechol, may result in strong neuroprotective activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.036

文献信息

• Interface coassembly of mesoporous MoS₂ based-frameworks for enhanced near-infrared light driven photocatalysis
  作者：Lihua Zhi、Haoli Zhang、Zhengyin Yang、Weisheng Liu、Baodui Wang

  DOI：10.1039/c6cc00780e

  日期：——

  The three-dimensional porous Fe₃O₄@Cu_2−xS–MoS₂ framework is reported for the first time. Such a hybrid framework exhibits excellent NIR-light photocatalytic activity and stable cycling for the direct arylation of heteroaromatics at room temperature.

  首次报道了三维多孔的Fe₃O₄@Cu_{2−xS–MoS2框架。这种混合框架展现出优异的近红外光光催化活性，并在室温下对杂环芳烃进行直接芳基化反应具有稳定的循环性能。}
• Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity
  作者：Maria Koufaki、Christina Kiziridi、Faidra Nikoloudaki、Michael N. Alexis

  DOI：10.1016/j.bmcl.2007.05.036

  日期：2007.8

  We designed and synthesized new analogues containing 1,2-dithiolane-3-alkyl and protected or free catechol moieties connected through heteroaromatic rings such as triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, tetrazole or thiazole in order to explore the influence of the bioisosteric replacement of the amide group on the neuroprotective activity of the lipoic acid/dopamine conjugate. Evaluation of the activity of the new compounds, using glutamate-challenged hippocampal HT22 cells, showed that incorporation of heteroaromatic rings in the alkyl-1,2-dithiolane moieties in conjunction with another antioxidant, in this case catechol, may result in strong neuroprotective activity. (c) 2007 Elsevier Ltd. All rights reserved.
• A dopamine-alpha-lipoic acid hybridization compound and its acetylated form inhibit LPS-mediated inflammation
  作者：Ji-Sun Hwang、Jeong-Mi An、Hyeongjin Cho、Seung Hwan Lee、Jeong-Ho Park、Inn-Oc Han

  DOI：10.1016/j.ejphar.2014.10.052

  日期：2015.1

  In the present study, we synthesized and evaluated the anti-inflammatory effects of dopamine and alpha-lipoic acid (ALA) hybrid compounds, ALA-dopamine (HBU-199) and its acetylated derivative, ALA-acetyl dopamine (HBU-200), in BV2 microglia and RAW264.7 macrophage cells. HBU-199 and HBU-200 both significantly and dose dependently inhibited LPS-induced nitric oxide (NO) productions, NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 and interleukin-1 beta mRNA expressions and iNOS and COX-2 protein expressions. Furthermore, HBU-199 and HBU-200 protected RAW264.7 cells from activation induced cell death. However, at same concentrations, dopamine or ALA did not inhibit LPS-medialed production of inflammatory molecules and activation induced cell death. HBU-199 and HBU-200 inhibited LPS-induced inhibition of inhibitory kappa-B-alpha (I kappa B-alpha) phosphorylalion and nuclear factor kappa B (NF-kappa B) activation. Furthermore, LPS mediated DNA binding of p65 and p50 to the NF-kappa B binding site of the iNOS promoter was inhibited by HBU-199 and HBU-200, whereas dopamine and ALA did not inhibit LPS induced NF-kappa B activation and I kappa B-alpha phosphorylalion. Moreover, HBU-199 and HBU-200 suppressed LPS stimulated phosphorylalion of Akt. but not glycogen synthase kinase 3 beta. Overall, our data suggest that the ALA-dopamine hybrid compounds down-regulate inflammatory responses via inhibition of NE-kappa B and NF-kappa B-dependent gene expression, suggesting that it is a promising therapeutic agent for both systemic inflammatory diseases and inflammatory diseases of central nervous system. (C) 2014 Elsevier B.V. All rights reserved.