O²-(2,4-dinitro-5-fluorophenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate | 903568-91-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O²-(2,4-dinitro-5-fluorophenyl) 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate
• 英文别名: (Z)-dimethylamino-(5-fluoro-2,4-dinitrophenoxy)imino-oxidoazanium
• CAS: 903568-91-2
• 化学式: C₈H₈FN₅O₆
• 分子量: 289.18
• InChiKey: MVJLIJLGZJUMSZ-UVTDQMKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 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：
  145
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-hydroxy-3,3-dimethyltriaz-1-ene 2-oxide sodium salt 、 1,5-二氟-2,4-二硝基苯 在 碳酸氢钠 作用下， 以 叔丁醇 为溶剂， 反应 0.25h， 以40%的产率得到O²-(2,4-dinitro-5-fluorophenyl) 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

• The Secondary Amine/Nitric Oxide Complex Ion R₂N[N(O)NO]^- as Nucleophile and Leaving Group in S_NAr Reactions
  作者：Joseph E. Saavedra、Aloka Srinivasan、Challice L. Bonifant、Jingxi Chu、Anna P. Shanklin、Judith L. Flippen-Anderson、William G. Rice、Jim A. Turpin、Keith M. Davies、Larry K. Keefer

  DOI：10.1021/jo0016529

  日期：2001.5.1

  the cis arrangement of the oxygens were confirmed by X-ray crystallography. Displacement by various nucleophiles showed R(2)N[N(O)NO](-) to be a reasonably good leaving group, with rate constants for displacement by hydroxide, methoxide, and isopropylamine that were between those of chloride and fluoride in the S(N)Ar reactions we surveyed. The Meisenheimer intermediate could be spectrally observed. These

  结构R（2）N [N（O）NO]（-）及其烷基化产物的离子已越来越多地用作生物医学研究应用中的一氧化氮（NO）生成剂。在这里我们表明，这样的重氮二氮杂阴离子可以很容易地从各种亲电氮杂或硝基芳族底物中取代卤化物，形成结构R（2）NN（O）= N-OAr的O（2）芳基化衍生物。通过X射线晶体学确认了氧的芳基化位点和顺式排列。各种亲核试剂的置换显示R（2）N [N（O）NO]（-）是一个较好的离去基团，其氢氧化物，甲醇盐和异丙胺的置换速率常数介于氯化物和氟化物中。我们调查了S（N）Ar反应。迈森海默中间体可以通过光谱观察到。
• 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.
• 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.