methyl 3-(3,4-dihydroxyphenyl)-2-(2-thioxo-1,3-dithiole-4-carboxamido)propanoate | 1235581-89-1

• 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: methyl 3-(3,4-dihydroxyphenyl)-2-(2-thioxo-1,3-dithiole-4-carboxamido)propanoate
• 英文别名: ACS 85；methyl (2S)-3-(3,4-dihydroxyphenyl)-2-[(2-sulfanylidene-1,3-dithiole-4-carbonyl)amino]propanoate
• CAS: 1235581-89-1
• 化学式: C₁₄H₁₃NO₅S₃
• 分子量: 371.459
• InChiKey: QICOFNLBWMBMSU-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  acide dithiole-1,3 thioxo-2 carboxylique-4 、 L-3,4-二羟基苯基丙氨酸甲酯盐酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以56%的产率得到methyl 3-(3,4-dihydroxyphenyl)-2-(2-thioxo-1,3-dithiole-4-carboxamido)propanoate
  参考文献：
  名称：

  Effects of Hydrogen Sulfide-releasing l-DOPA Derivatives on Glial Activation

  摘要：

  The main lesion in Parkinson disease (PD) is loss of substantia nigra dopaminergic neurons. Levodopa (L-DOPA) is the most widely used therapy, but it does not arrest disease progression. Some possible contributing factors to the continuing neuronal loss are oxidative stress, including oxidation of L-DOPA, and neurotoxins generated by locally activated microglia and astrocytes. A possible method of reducing these factors is to produce L-DOPA hybrid compounds that have antioxidant and anti-inflammatory properties. Here we demonstrate the properties of four such L-DOPA hybrids based on coupling L-DOPA to four different hydrogen sulfide-donating compounds. The donors themselves were shown to be capable of conversion by isolated mitochondria to H2S or equivalent SH- ions. This capability was confirmed by in vivo results, showing a large increase in intracerebral dopamine and glutathione after iv administration in rats. When human microglia, astrocytes, and SH-SY5Y neuroblastoma cells were treated with these donating agents, they all accumulated H2S intracellularly as did their derivatives coupled to L-DOPA. The donating agents and the L-DOPA hybrids reduced the release of tumor necrosis factor-alpha, interleukin-6, and nitric oxide from stimulated microglia, astrocytes as well as the THP-1 and U373 cell lines. They also demonstrated a neuroprotective effect by reducing the toxicity of supernatants from these stimulated cells to SH-SY5Y cells. L-DOPA itself was without effect in any of these assays. The H2S-releasing L-DOPA hybrid molecules also inhibited MAO B activity. They may be useful for the treatment of PD because of their significant anti-inflammatory, antioxidant, and neuroprotective properties.

  DOI：

  10.1074/jbc.m110.115261

文献信息

• Effects of Hydrogen Sulfide-releasing l-DOPA Derivatives on Glial Activation
  作者：Moonhee Lee、Valerio Tazzari、Daniela Giustarini、Ranieri Rossi、Anna Sparatore、Piero Del Soldato、Edith McGeer、Patrick L. McGeer

  DOI：10.1074/jbc.m110.115261

  日期：2010.6

  The main lesion in Parkinson disease (PD) is loss of substantia nigra dopaminergic neurons. Levodopa (L-DOPA) is the most widely used therapy, but it does not arrest disease progression. Some possible contributing factors to the continuing neuronal loss are oxidative stress, including oxidation of L-DOPA, and neurotoxins generated by locally activated microglia and astrocytes. A possible method of reducing these factors is to produce L-DOPA hybrid compounds that have antioxidant and anti-inflammatory properties. Here we demonstrate the properties of four such L-DOPA hybrids based on coupling L-DOPA to four different hydrogen sulfide-donating compounds. The donors themselves were shown to be capable of conversion by isolated mitochondria to H2S or equivalent SH- ions. This capability was confirmed by in vivo results, showing a large increase in intracerebral dopamine and glutathione after iv administration in rats. When human microglia, astrocytes, and SH-SY5Y neuroblastoma cells were treated with these donating agents, they all accumulated H2S intracellularly as did their derivatives coupled to L-DOPA. The donating agents and the L-DOPA hybrids reduced the release of tumor necrosis factor-alpha, interleukin-6, and nitric oxide from stimulated microglia, astrocytes as well as the THP-1 and U373 cell lines. They also demonstrated a neuroprotective effect by reducing the toxicity of supernatants from these stimulated cells to SH-SY5Y cells. L-DOPA itself was without effect in any of these assays. The H2S-releasing L-DOPA hybrid molecules also inhibited MAO B activity. They may be useful for the treatment of PD because of their significant anti-inflammatory, antioxidant, and neuroprotective properties.