O²-(2,4-dinitro-5-hydroxyphenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate | 903568-92-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: O²-(2,4-dinitro-5-hydroxyphenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate
• 英文别名: (Z)-dimethylamino-(5-hydroxy-2,4-dinitrophenoxy)imino-oxidoazanium
• CAS: 903568-92-3
• 化学式: C₈H₉N₅O₇
• 分子量: 287.189
• InChiKey: BCGQBRJDDFYDBC-LCYFTJDESA-N

物化性质

• 熔点：
  105-106 °C(Solv: ethyl ether (60-29-7); ligroine (8032-32-4))
• 沸点：
  445.2±55.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  165
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  O²-(2,4-dinitro-5-hydroxyphenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate 、 邻乙酰水杨酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到(Z)-[5-(2-acetyloxybenzoyl)oxy-2,4-dinitrophenoxy]imino-(dimethylamino)-oxidoazanium
  参考文献：
  名称：

  Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound

  摘要：

  Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O-2-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl)-1-(N,N-dimetliylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O-2-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.035
• 作为产物：
  描述：

  O²-(2,4-dinitro-5-fluorophenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate 在 sodium hydroxide 作用下， 以 叔丁醇 为溶剂， 反应 1.5h， 生成 O²-(2,4-dinitro-5-hydroxyphenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Antitumor Activity of JS-K [O²-(2,4-Dinitrophenyl) 1-[(4-Ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and Related O²-Aryl Diazeniumdiolates in Vitro and in Vivo

  摘要：

  The literature provides evidence that metabolic nitric oxide ( NO) release mediates the cytotoxic activities ( against human leukemia and prostate cancer xenografts in mice) of JS-K, a compound of structure R2N-(O)=NO-Ar for which R2N is 4-(ethoxycarbonyl) piperazin-1-yl and Ar is 2,4-dinitrophenyl. Here we present comparative data on the potencies of JS-K and 41 other O-2-arylated diazeniumdiolates as inhibitors of HL-60 human leukemia cell proliferation, as well as in the NCI 51-cell-line screen for six of them. The data show JS-K to be the most potent of the 42 in both screens and suggest that other features of its structure and metabolism besides NO release may contribute importantly to its activity. Results with control compounds implicate JS-K's arylating ability, and the surprisingly low IC50 value of the N-(ethoxycarbonyl) piperazine byproduct of NO release suggests a role for the R2N moiety. In addition to the above-mentioned in vivo activities, JS-K is shown here to be carcinostatic in a rat liver cancer model.

  DOI：

  10.1021/jm060022h

文献信息

• Antitumor Activity of JS-K [<i>O</i>²-(2,4-Dinitrophenyl) 1-[(4-Ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] and Related <i>O</i>²-Aryl Diazeniumdiolates in Vitro and in Vivo
  作者：Paul J. Shami、Joseph E. Saavedra、Challice L. Bonifant、Jingxi Chu、Vidya Udupi、Swati Malaviya、Brian I. Carr、Siddhartha Kar、Meifeng Wang、Lee Jia、Xinhua Ji、Larry K. Keefer

  DOI：10.1021/jm060022h

  日期：2006.7.1

  The literature provides evidence that metabolic nitric oxide ( NO) release mediates the cytotoxic activities ( against human leukemia and prostate cancer xenografts in mice) of JS-K, a compound of structure R2N-(O)=NO-Ar for which R2N is 4-(ethoxycarbonyl) piperazin-1-yl and Ar is 2,4-dinitrophenyl. Here we present comparative data on the potencies of JS-K and 41 other O-2-arylated diazeniumdiolates as inhibitors of HL-60 human leukemia cell proliferation, as well as in the NCI 51-cell-line screen for six of them. The data show JS-K to be the most potent of the 42 in both screens and suggest that other features of its structure and metabolism besides NO release may contribute importantly to its activity. Results with control compounds implicate JS-K's arylating ability, and the surprisingly low IC50 value of the N-(ethoxycarbonyl) piperazine byproduct of NO release suggests a role for the R2N moiety. In addition to the above-mentioned in vivo activities, JS-K is shown here to be carcinostatic in a rat liver cancer model.
• Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound
  作者：Harinath Chakrapani、Thomas C. Wilde、Michael L. Citro、Michael M. Goodblatt、Larry K. Keefer、Joseph E. Saavedra

  DOI：10.1016/j.bmc.2007.11.035

  日期：2008.3

  Diazeniumdiolate anions and their prodrug forms are reliable sources of nitric oxide (NO) that have generated interest as promising therapeutic agents. A number of structural analogues of O-2-(2,4-dinitro-5-(4-(N-methylamino)benzoyloxy)phenyl)-1-(N,N-dimetliylamino)diazen-1-ium-1,2-diolate (PABA/NO), an anti-cancer lead compound that is designed to release NO upon activation by glutathione, were prepared. The nitric oxide release patterns of these O-2-(2,4-dinitrophenyl) diazeniumdiolates in the presence of glutathione were tested and it was found that in the absence of competing pathways, these compounds release nearly quantitative amounts of NO. The ability of PABA/NO and its structural analogues to inhibit human leukemia cell proliferation was determined and it was found that compounds releasing elevated amounts of NO displayed superior cytotoxic effects. (C) 2007 Elsevier Ltd. All rights reserved.