diethyl (((4-hydroxyphenyl)sulfonyl)methyl)phosphonate | 211518-82-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl (((4-hydroxyphenyl)sulfonyl)methyl)phosphonate
• 英文别名: 4-hydroxy-thiophenyl-methyl-diethylphosphonate sulfone；4-(diethoxyphosphorylmethylsulfonyl)phenol
• CAS: 211518-82-0
• 化学式: C₁₁H₁₇O₆PS
• 分子量: 308.292
• InChiKey: MDWIDKAPUZOYOH-UHFFFAOYSA-N

物化性质

• 沸点：
  499.3±45.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  diethyl (((4-hydroxyphenyl)sulfonyl)methyl)phosphonate 在 盐酸 、 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 环己烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 4.5h， 生成 (E)-4-(3-(4-((2-(2′-chloropyridine-3′-yl)vinyl)sulfonyl)phenoxy)propyl)morpholine hydrochloride
  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
• 作为产物：
  描述：

  羟甲基膦酸二乙酯 在 caesium carbonate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 diethyl (((4-hydroxyphenyl)sulfonyl)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

文献信息

• Solid-Phase Synthesis of Peptide Vinyl Sulfones as Potential Inhibitors and Activity-Based Probes of Cysteine Proteases
  作者：Gang Wang、Uttamchandani Mahesh、Grace Y. J. Chen、Shao Q. Yao

  DOI：10.1021/ol0275567

  日期：2003.3.1

  Peptide vinyl sulfones were prepared from 2-chlorotrityl resin-bound phenolic amino vinyl sulfones in high yield and purity. This method enables the convenient synthesis of peptide vinyl sulfones having different amino acids at the P(1) position. It also allows efficient synthesis of vinyl sulfone-containing, activity-based probes of cysteine proteases used in a proteomic experiment.

  由2-氯三苯甲基树脂结合的酚氨基乙烯基乙烯基砜以高收率和纯度制备了肽乙烯基砜。该方法能够方便地合成在P（1）位置具有不同氨基酸的肽乙烯基砜。它还可以有效合成蛋白质组学实验中使用的含乙烯基砜，基于活性的半胱氨酸蛋白酶探针。
• Proteomic profiling and potential cellular target identification of K11777, a clinical cysteine protease inhibitor, in Trypanosoma brucei
  作者：Peng-Yu Yang、Min Wang、Cynthia Y. He、Shao Q. Yao

  DOI：10.1039/c1cc16178d

  日期：——

  We report herein the design, synthesis and application of K11777-derived activity-based probes (ABPs) allowing in situ profiling and identification of potential cellular targets of K11777 in Trypanosoma brucei.

  我们在此报告了K11777衍生的基于活性的探针（ABPs）的设计、合成和应用，这些探针可以在体内分析和识别K11777在锥虫（Trypanosoma brucei）中的潜在细胞靶点。
• EP3838896
  申请人：——

  公开号：——

  公开（公告）日：——
• NOVEL HALO-(3-(PHENYLSULFONYL)PROP-1-ENYL)PYRIDINE DERIVATIVE AND USE THEREOF
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20210317083A1

  公开（公告）日：2021-10-14

  The present invention relates to a novel halo-(3-(phenylsulfonyl)prop-1-enyl)pyridine derivative or a pharmaceutically acceptable salt thereof; a preparation method thereof; and an Nrf2 activator and a pharmaceutical composition for preventing or treating diseases induced by a decrease in Nrf2 activity, both of which comprise the same as an active ingredient.