(2,4-dinitrophenoxy)imino-(4-ethoxycarbonyl-2-methylpiperazin-1-yl)-oxidoazanium | 1083256-00-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (2,4-dinitrophenoxy)imino-(4-ethoxycarbonyl-2-methylpiperazin-1-yl)-oxidoazanium
• CAS: 1083256-00-1
• 化学式: C₁₄H₁₈N₆O₈
• 分子量: 398.332
• InChiKey: GCIYZIRJJOUIEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  175
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  sodium 1-[4-ethoxycarbonyl-2-methylpiperazin-1-yl]diazen-1-ium-1,2-diolate 、 2,4-二硝基氟苯 在 碳酸氢钠 作用下， 以 叔丁醇 为溶剂， 生成 (2,4-dinitrophenoxy)imino-(4-ethoxycarbonyl-2-methylpiperazin-1-yl)-oxidoazanium
  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

• 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.