2-甲基-1,4-哌嗪二甲酸二乙酯 | 63981-45-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-甲基-1,4-哌嗪二甲酸二乙酯
• 英文名称: 2-methyl-1,4-bis(ethoxycarbonyl)piperazine
• 英文别名: 2-methyl-piperazine-1,4-dicarboxylic acid diethyl ester；2-Methyl-piperazin-1,4-dicarbonsaeure-diaethylester；1,4-Dicarbethoxy-2-methylpiperazine；diethyl 2-methylpiperazine-1,4-dicarboxylate
• CAS: 63981-45-3
• 化学式: C₁₁H₂₀N₂O₄
• 分子量: 244.291
• InChiKey: NEUYJXYCELJYTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲基-1,4-哌嗪二甲酸二乙酯 在 氢氧化钾 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以57%的产率得到乙基2-甲基-1-哌嗪羧酸酯
  参考文献：
  名称：

  Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs

  摘要：

  Nitric oxide (NO) prodrugs such as O-2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.09.063
• 作为产物：
  描述：

  2-甲基哌嗪 、 氯甲酸乙酯 在 三乙胺盐酸盐 、 三乙胺 作用下， 以66%的产率得到2-甲基-1,4-哌嗪二甲酸二乙酯
  参考文献：
  名称：

  Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs

  摘要：

  Nitric oxide (NO) prodrugs such as O-2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.09.063

文献信息

• EXPERIMENTAL CHEMOTHERAPY OF FILARIASIS. IV. THE PREPARATION OF DERIVATIVES OF PIPERAZINE¹
  作者：H. W. STEWART、R. J. TURNER、J. J. DENTON、S. KUSHNER、L. M. BRANCONE、W. L. McEWEN、R. I. HEWITT、Y. SUBBAROW

  DOI：10.1021/jo01159a018

  日期：1948.1
• Synthesis, mechanistic studies, and anti-proliferative activity of glutathione/glutathione S-transferase-activated nitric oxide prodrugs
  作者：Harinath Chakrapani、Ravi C. Kalathur、Anna E. Maciag、Michael L. Citro、Xinhua Ji、Larry K. Keefer、Joseph E. Saavedra

  DOI：10.1016/j.bmc.2008.09.063

  日期：2008.11

  Nitric oxide (NO) prodrugs such as O-2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) are a growing class of promising NO-based therapeutics. Nitric oxide release from the anti-cancer lead compound, JS-K, is proposed to occur through a nucleophilic aromatic substitution by glutathione (GSH) catalyzed by glutathione S-transferase (GST) to form a diazeniumdiolate anion that spontaneously releases NO. In this study, a number of structural analogues of JS-K were synthesized and their chemical and biological properties were compared with those of JS-K. The homopiperazine analogue of JS-K showed anti-cancer activity that is comparable with that of JS-K but with a diminished reactivity towards both GSH and GSH/GST; both the aforementioned compounds displayed no cytotoxic activity towards normal renal epithelial cell line at concentrations where they significantly diminished the proliferation of a panel of renal cancer cell lines. These properties may prove advantageous in the further development of this class of nitric oxide prodrugs as cancer therapeutic agents. Published by Elsevier Ltd.