N-hydroxy-N-methylcarbamate thioethyl ester | 22414-30-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫基化合物
• 英文名称: N-hydroxy-N-methylcarbamate thioethyl ester
• 英文别名: S-ethyl hydroxy(methyl)carbamothioate；N-Methyl-N-(ethyl-mercaptocarbonyl)-hydroxylamin；S-ethyl N-hydroxy-N-methylcarbamothioate
• CAS: 22414-30-8
• 化学式: C₄H₉NO₂S
• 分子量: 135.187
• InChiKey: XLYAZHDSRRWCQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-hydroxy-N-methylcarbamate thioethyl ester 在 间氯过氧苯甲酸 作用下， 以 乙醚 为溶剂， 反应 0.5h， 以86%的产率得到1-ethylsulfinyl-N-hydroxy-N-methylformamide
  参考文献：
  名称：

  A New Method for Rapidly Generating Inhibitors of Glyoxalase I inside Tumor Cells Using S-(N-Aryl-N-hydroxycarbamoyl)ethylsulfoxides

  摘要：

  The enediol analogue S-(N-p-chlorophenyl-N-hydroxycarbamoyl)glutathione is a powerful mechanism-based competitive inhibitor of the anticancer target enzyme glyoxalase I. Nevertheless, this compound exhibits limited toxicity toward tumor cells in vitro because it does not readily diffuse across cell membranes. We describe an efficient method for indirectly delivering the enzyme inhibitor into murine leukemia L1210 cells via acyl interchange between intracellular glutathione and the cell-permeable prodrug S-(N-p-chlorophenyl-N-hydroxycarbamoyl)ethylsulfoxide. The second-order rate constant for the acyl-interchange reaction in a cell-free system is 1.84 mM(-1) min(-1) (100 mM potassium phosphate buffer, 5% ethanol, pH 7.5, 25 degrees C). Incubation of L1210 cells with the sulfoxide in vitro results in a rapid increase in the intracellular concentration of the glyoxalase I inhibitor (k(app) = 1.41 +/- 0.03 min(-1) (37 degrees C)) and inhibition of cell growth (GI(50) = 0.5 +/- 0.1 mu M). This represents an improvement in both efficiency and potency over the dialkyl ester prodrug strategy in which the inhibitor is indirectly delivered into tumor cells as the [glycyl,glutamyl] diethyl or dicyclopentyl esters. The fact that pi-glutathione transferase catalyzes the acyl-interchange reaction between GSH and the sulfoxide suggests that the sulfoxide, or related compounds, might exhibit greater selective toxicity toward tumor cells that overexpress the transferase.

  DOI：

  10.1021/jm980712o
• 作为产物：
  描述：

  N-甲基羟胺 、 硫代氯甲酸乙酯 在 potassium carbonate 作用下， 以 乙醚 为溶剂， 以70%的产率得到N-hydroxy-N-methylcarbamate thioethyl ester
  参考文献：
  名称：

  A New Method for Rapidly Generating Inhibitors of Glyoxalase I inside Tumor Cells Using S-(N-Aryl-N-hydroxycarbamoyl)ethylsulfoxides

  摘要：

  The enediol analogue S-(N-p-chlorophenyl-N-hydroxycarbamoyl)glutathione is a powerful mechanism-based competitive inhibitor of the anticancer target enzyme glyoxalase I. Nevertheless, this compound exhibits limited toxicity toward tumor cells in vitro because it does not readily diffuse across cell membranes. We describe an efficient method for indirectly delivering the enzyme inhibitor into murine leukemia L1210 cells via acyl interchange between intracellular glutathione and the cell-permeable prodrug S-(N-p-chlorophenyl-N-hydroxycarbamoyl)ethylsulfoxide. The second-order rate constant for the acyl-interchange reaction in a cell-free system is 1.84 mM(-1) min(-1) (100 mM potassium phosphate buffer, 5% ethanol, pH 7.5, 25 degrees C). Incubation of L1210 cells with the sulfoxide in vitro results in a rapid increase in the intracellular concentration of the glyoxalase I inhibitor (k(app) = 1.41 +/- 0.03 min(-1) (37 degrees C)) and inhibition of cell growth (GI(50) = 0.5 +/- 0.1 mu M). This represents an improvement in both efficiency and potency over the dialkyl ester prodrug strategy in which the inhibitor is indirectly delivered into tumor cells as the [glycyl,glutamyl] diethyl or dicyclopentyl esters. The fact that pi-glutathione transferase catalyzes the acyl-interchange reaction between GSH and the sulfoxide suggests that the sulfoxide, or related compounds, might exhibit greater selective toxicity toward tumor cells that overexpress the transferase.

  DOI：

  10.1021/jm980712o

文献信息

• Visible-Light-Mediated Synthesis of Amidyl Radicals: Transition-Metal-Free Hydroamination and <i>N</i>-Arylation Reactions
  作者：Jacob Davies、Thomas D. Svejstrup、Daniel Fernandez Reina、Nadeem S. Sheikh、Daniele Leonori

  DOI：10.1021/jacs.6b04920

  日期：2016.7.6

  The development of photoredox reactions of aryloxy-amides for the generation of amidyl radicals and their use in hydroamination-cyclization and N-arylation reactions is reported. Owing to the ease of single-electron-transfer reduction of the aryloxy-amides, the organic dye eosin Y was used as the photoredox catalyst, which results in fully transition-metal-free processes. These transformations exhibit

  报道了芳氧基-酰胺光氧化还原反应产生酰胺基自由基的发展及其在加氢胺化-环化和 N-芳基化反应中的应用。由于芳氧基酰胺易于单电子转移还原，有机染料伊红 Y 被用作光氧化还原催化剂，这导致完全无过渡金属的过程。这些转变表现出广泛的范围，可以容忍几个重要的功能，并已用于复杂和高价值含氮分子的后期修饰。
• Baskakov,Yu.A. et al., Journal of Organic Chemistry USSR (English Translation), 1968, vol. 4, p. 2062 - 2065
  作者：Baskakov,Yu.A. et al.

  DOI：——

  日期：——
• A New Method for Rapidly Generating Inhibitors of Glyoxalase I inside Tumor Cells Using <i>S</i>-(<i>N</i>-Aryl-<i>N</i>-hydroxycarbamoyl)ethylsulfoxides
  作者：Diana S. Hamilton、Malcolm J. Kavarana、Ellyn M. Sharkey、Julie L. Eiseman、Donald J. Creighton

  DOI：10.1021/jm980712o

  日期：1999.5.1

  The enediol analogue S-(N-p-chlorophenyl-N-hydroxycarbamoyl)glutathione is a powerful mechanism-based competitive inhibitor of the anticancer target enzyme glyoxalase I. Nevertheless, this compound exhibits limited toxicity toward tumor cells in vitro because it does not readily diffuse across cell membranes. We describe an efficient method for indirectly delivering the enzyme inhibitor into murine leukemia L1210 cells via acyl interchange between intracellular glutathione and the cell-permeable prodrug S-(N-p-chlorophenyl-N-hydroxycarbamoyl)ethylsulfoxide. The second-order rate constant for the acyl-interchange reaction in a cell-free system is 1.84 mM(-1) min(-1) (100 mM potassium phosphate buffer, 5% ethanol, pH 7.5, 25 degrees C). Incubation of L1210 cells with the sulfoxide in vitro results in a rapid increase in the intracellular concentration of the glyoxalase I inhibitor (k(app) = 1.41 +/- 0.03 min(-1) (37 degrees C)) and inhibition of cell growth (GI(50) = 0.5 +/- 0.1 mu M). This represents an improvement in both efficiency and potency over the dialkyl ester prodrug strategy in which the inhibitor is indirectly delivered into tumor cells as the [glycyl,glutamyl] diethyl or dicyclopentyl esters. The fact that pi-glutathione transferase catalyzes the acyl-interchange reaction between GSH and the sulfoxide suggests that the sulfoxide, or related compounds, might exhibit greater selective toxicity toward tumor cells that overexpress the transferase.