sodium 1-(4-ethyloxylcarbonylpiperazine-1-yl)diazen-1-ium-1,2-diolate | 178948-49-7

• 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: sodium 1-(4-ethyloxylcarbonylpiperazine-1-yl)diazen-1-ium-1,2-diolate
• 英文别名: sodium 1-(4-ethoxycarbonylpiperazin-1-yl)diazen-1-ium-1,2-diolate；1-[4-(ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate
• CAS: 178948-49-7
• 化学式: C₇H₁₃N₄O₄*Na
• 分子量: 240.194
• InChiKey: JEZQVYRUIBUOCU-UHFFFAOYSA-M

物化性质

• 熔点：
  184-185 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -2.86
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  94.27
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  sodium 1-(4-ethyloxylcarbonylpiperazine-1-yl)diazen-1-ium-1,2-diolate 在 15-冠醚-5 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 O2-(3,4,6-tri-O-acetyl-β-D-N-acetylglucosaminyl) 1-[4(ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Novel protection–deprotection strategies in diazeniumdiolate chemistry: synthesis of V-IPA/NO

  摘要：

  本文报道了先前无法合成、可能具有肝脏选择性的HNO供体V-IPA/NO（[iPrHN3–N1(O1)N2–O2–R]，其中R = 乙烯基）的合成方法。在IPA/NO的O-2位引入新型氟化物敏感的TOM保护基团，同时在N-3上采用MOM保护。该策略还扩展到其他释放NO的前药的合成，并应用于多样化合成HNO和NO前药的领域。

  DOI：

  10.1039/c1cc12130h
• 作为产物：
  描述：

  N-哌嗪甲酸乙酯 在 titanium(IV) oxide 、 氧化亚氮 、 sodium methylate 作用下， 以 甲醇 、 乙醚 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 48.0h， 生成 sodium 1-(4-ethyloxylcarbonylpiperazine-1-yl)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  O 2-（2,4-二硝基苯基）二氮杂二烯二醇盐和齐墩果酸的杂化分子：谷胱甘肽S-转移酶π-活化的一氧化氮前药，具有选择性的抗人肝细胞癌活性和更高的稳定性

  摘要：

  设计，合成并合成了O 2-（2,4-二硝基苯基）二氮杂二烯二醇盐和齐墩果酸（OA）的一系列杂种，并将其作为可被谷胱甘肽S-转移酶π激活的新型释放一氧化氮（NO）的前药进行了生物学评估。（GSTπ）在许多癌细胞中过表达。发现活性最高的化合物21在HCC细胞中选择性释放高水平的NO，而在正常细胞中则不释放，并且在体外表现出有效的抗增殖活性以及体内显着的肿瘤延缓作用。与报道的GSTπ活化的前药JS-K和PABA / NO相比，在不存在GSTπ的情况下21显示出显着改善的稳定性。重要的是，分解21在谷胱甘肽S-转移酶存在下发生，比谷胱甘肽S-转移酶α有效得多。此外，21通过诱导细胞周期停滞在G2 / M期，激活线粒体介导的途径和MAPK途径，并增强ROS的细胞内产生，从而诱导HepG2细胞凋亡。

  DOI：

  10.1021/jm400393u

文献信息

• [EN] DUAL ACTION NITRIC OXIDE DONORS AND THEIR USE AS ANTIMICROBIAL AGENTS<br/>[FR] DONNEURS D'OXYDE NITRIQUE À DOUBLE ACTION ET LEUR UTILISATION COMME AGENTS ANTIMICROBIENS
  申请人：NEWSOUTH INNOVATIONS PTY LTD

  公开号：WO2014071457A1

  公开（公告）日：2014-05-15

  The present invention relates generally to conjugates comprising a nitric oxide donor and an acyl homoserine lactone, fimbrolide, fimbrolide derivative, dihydropyrrolone or indole, and to the use of such conjugates as antimicrobial agents.

  本发明涉及一般地与一氧化氮供体和酰基同源丁氨酸内酯、菲螺啉、菲螺啉衍生物、二氢吡咯酮或吲哚构成的结合物，以及将这些结合物用作抗微生物剂的用途。
• 一种过氧化氢响应的偶氮鎓二醇盐类化合物 及其用途
  申请人：江南大学

  公开号：CN110577504B

  公开（公告）日：2021-05-28

  本发明公开了一种过氧化氢响应的偶氮鎓二醇盐类化合物及其用途，属于药物化学领域。本发明化合物稳定性高，其α‑酮酰胺结构可特异性响应H2O2释放NO，不同的结构可实现对不同种类肿瘤细胞的特异性抑制，且对正常细胞毒性小，可作为一类肿瘤细胞选择性高、毒副作用小的新型NO供体型药物，具有很好的市场前景。
• Novel α-ketoamide based diazeniumdiolates as hydrogen peroxide responsive nitric oxide donors with anti-lung cancer activity
  作者：Junjie Fu、Jing Han、Tingting Meng、Jing Hu、Jian Yin

  DOI：10.1039/c9cc05266f

  日期：——

  A novel type of hydrogen peroxide (H2O2)-activated diazeniumdiolate based on an α-ketoamide moietey was developed as a nitric oxide (NO) donor. KA-NO-4 inhibited lung cancer cells with submicromolar activity. The H2O2-responsive behaviour of KA-NO-4 was thoroughly investigated. The NO-centered mechanism of action of KA-NO-4 was intracellularly studied.

  开发了一种新型的基于α-酮酰胺基的过氧化氢（H 2 O 2）活化的二醇二氮烯二酸酯作为一氧化氮（NO）供体。KA-NO-4抑制具有亚微摩尔活性的肺癌细胞。彻底研究了KA-NO-4的H 2 O 2响应行为。在细胞内研究了以NO为中心的KA-NO-4的作用机理。
• Hydrolytic Reactivity Trends among Potential Prodrugs of the O²-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity
  作者：Carlos A. Valdez、Joseph E. Saavedra、Brett M. Showalter、Keith M. Davies、Thomas C. Wilde、Michael L. Citro、Joseph J. Barchi、Jeffrey R. Deschamps、Damon Parrish、Stefan El-Gayar、Ulrike Schleicher、Christian Bogdan、Larry K. Keefer

  DOI：10.1021/jm8000482

  日期：2008.7

  Glycosylated diazeniumdiolates of structure R(2)NN(O)=NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R(2)NN(O)=NO(-) ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R(2)NN(O)=NO-GlcNAc (where R(2)N = diethylamino or pyrrolidin-1-yl and GlcNAc = N-acetylglucosamin-1-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.
• 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.