JS-59-4 | 1309040-90-1

• 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: JS-59-4
• 英文别名: (2-Cyano-4-nitrophenoxy)imino-(4-ethoxycarbonylpiperazin-1-yl)-oxidoazanium；(2-cyano-4-nitrophenoxy)imino-(4-ethoxycarbonylpiperazin-1-yl)-oxidoazanium
• CAS: 1309040-90-1
• 化学式: C₁₄H₁₆N₆O₆
• 分子量: 364.318
• InChiKey: CRQUIISEMQYDFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  153
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  谷胱甘肽 、 JS-59-4 在 二乙烯三胺五醋酸 作用下， 生成 2-(S-Glutathionyl)-5-nitrobenzonitrile
  参考文献：
  名称：

  Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs

  摘要：

  JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo anti-tumor activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.045
• 作为产物：
  描述：

  sodium 1-(4-ethyloxylcarbonylpiperazine-1-yl)diazen-1-ium-1,2-diolate 、 2-氟-5-硝基苯腈 以 四氢呋喃 、 二甲基亚砜 为溶剂， 以88%的产率得到JS-59-4
  参考文献：
  名称：

  Structural modifications modulate stability of glutathione-activated arylated diazeniumdiolate prodrugs

  摘要：

  JS-K, a diazeniumdiolate-based nitric oxide (NO)-releasing prodrug, is currently in late pre-clinical development as an anti-cancer drug candidate. This prodrug was designed to be activated by glutathione (GSH) to release NO. To increase the potency of JS-K, we are investigating the effect of slowing the reaction of the prodrugs with GSH. Herein, we report the effect of replacement of nitro group(s) by other electron-withdrawing group(s) in JS-K and its homo-piperazine analogues on GSH activation and the drugs' biological activity. We show that nitro-to-cyano substitution increases the half-life of the prodrug in the presence of GSH without compromising the compound's in vivo anti-tumor activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.045