diethyl (((3-methoxyphenyl)thio)methyl)phosphonate | 1478586-07-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: diethyl (((3-methoxyphenyl)thio)methyl)phosphonate
• 英文别名: 1-(Diethoxyphosphorylmethylsulfanyl)-3-methoxybenzene
• CAS: 1478586-07-0
• 化学式: C₁₂H₁₉O₄PS
• 分子量: 290.32
• InChiKey: ODLZDQHOQFOBCE-UHFFFAOYSA-N

物化性质

• 沸点：
  386.6±27.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (((3-methoxyphenyl)thio)methyl)phosphonate 在 正丁基锂 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 环己烷 为溶剂， 反应 4.0h， 生成 (E)-1-(2-((3-methoxyphenyl)sulfonyl)vinyl)-3-trifluoromethylbenzene
  参考文献：
  名称：

  Discovery of Vinyl Sulfones as a Novel Class of Neuroprotective Agents toward Parkinson’s Disease Therapy

  摘要：

  Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2, signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.

  DOI：

  10.1021/jm401788m
• 作为产物：
  描述：

  羟甲基膦酸二乙酯 在 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 diethyl (((3-methoxyphenyl)thio)methyl)phosphonate
  参考文献：
  名称：

  Optimization of Vinyl Sulfone Derivatives as Potent Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for Parkinson’s Disease Therapy

  摘要：

  We previously developed a novel series of vinyl sulfones as nuclear factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic potential for Parkinson's disease (PD). However, the previously developed lead compound (1) exhibited undesirable druglike properties. Here, we optimized vinyl sulfones by introducing nitrogen heterocycles to improve druglike properties. Among the synthesized compounds, 17e was the most promising drug candidate with good druglike properties. Compound 17e showed superior effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration (EC50) = 346 nM; 1: EC50 = 530 nM). Compound 17e was further confirmed to induce expression of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties and represents a potential therapeutic candidate for PD.

  DOI：

  10.1021/acs.jmedchem.8b01527