1,1-二乙基-2-羟基-2-亚硝基-肼钠 | 86831-65-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1,1-二乙基-2-羟基-2-亚硝基-肼钠
• 英文名称: 1-(N,N-diethylamino)-diazen-1-ium-1,2-dienolate
• 英文别名: 2-(N,N-diethylamino)-diazenolate-2-oxide；2-(N,N-diethylamino)diazenolate 2-oxide；2-(N,N-diethylamino)diazenolate-2-oxide；diethylaminodiazen-1-um-1,2-diolate；isopropylamine diazeniumdiolate；DEA-NONOate；1,1-Diethyl-2-hydroxy-2-nitrosohydrazine；N-(diethylamino)-N-oxidonitrous amide
• CAS: 86831-65-4
• 化学式: C₄H₁₀N₃O₂
• 分子量: 132.142
• InChiKey: VFZXVONSQCNCAT-UHFFFAOYSA-N

物化性质

• 熔点：
  45 °C(lit.)
• 溶解度：
  H2O: >10 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-bis(4-(bromomethyl)phenyl)disulfane 、 1,1-二乙基-2-羟基-2-亚硝基-肼钠 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  抗CD24抗体-一氧化氮选择性并有效地抑制肝癌。

  摘要：

  一氧化氮（NO）在肿瘤治疗中具有广泛的潜在应用。但是，针对NO供体的靶向递送系统仍然难以捉摸，从而形成了限制其可药物性的瓶颈。抗体-药物偶联物（ADC）是一种靶向药物递送系统，由与活性细胞毒性药物连接的抗体组成。该设计可以补偿NO供体的弱靶向能力和各种生物学功能。在这项研究中，我们设计了NO供体HL-2，它具有靶向的，裂解的二硫键和可连接的马来酰亚胺末端。我们将HL-2与通过硫醚键靶向CD24的抗体缀合，以生成ADC样的免疫缀合物，抗体-一氧化氮缀合物（ANC），我们将其命名为HN-01。HN-01表现出有效的内化作用，并显着增加了体外肝癌细胞中NO的释放。HN-01通过抗体依赖性共同毒性诱导荷肝癌裸鼠的肿瘤细胞凋亡并抑制肿瘤生长；HN-01还增加了肿瘤细胞中的NO水平。总的来说，这项研究扩展了ADC的概念，并提供了创新的NO供体和ANC，以解决NO定向输送中的当前挑战。ANC设计的这一新

  DOI：

  10.1158/0008-5472.can-18-2839
• 作为产物：
  描述：

  O²-(acetylsalicyloyloxymethyl)-1-(N,N-diethylamino)-diazen-1-ium-1,2-diolate 以 重水 为溶剂， 反应 90.0h， 生成 乙酸盐 、 1,1-二乙基-2-羟基-2-亚硝基-肼钠 、 阿司匹林
  参考文献：
  名称：

  Synthesis and Chemical and Biological Comparison of Nitroxyl- and Nitric Oxide-Releasing Diazeniumdiolate-Based Aspirin Derivatives

  摘要：

  Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.

  DOI：

  10.1021/jm400196q

文献信息

• Mechanistic Studies on the Reaction between R₂N-NONOates and Aquacobalamin: Evidence for Direct Transfer of a Nitroxyl Group from R₂N-NONOates to Cobalt(III) Centers
  作者：Hanaa���A. Hassanin、Luciana Hannibal、Donald���W. Jacobsen、Mohamed���F. El-Shahat、Mohamed���S.���A. Hamza、Nicola���E. Brasch

  DOI：10.1002/anie.200904360

  日期：2009.11.9

  Tales of the unexpected: Transfer of a nitroxyl group from R2N‐NONOates to aquacobalamin to form nitroxylcobalamin does not proceed via H+‐catalyzed R2N‐NONOate decomposition, but instead occurs via a probable NONOate‐cobalamin intermediate (see scheme; r.d.s.=rate‐determining step).

  出人意料的故事：硝酰基从 R 2 N-NONOate 转移到 aquacobalamin 以形成硝基钴胺素不是通过 H +催化的 R 2 N-NONOate 分解进行，而是通过可能的 NONOate-钴胺素中间体发生（参见方案； rds=速率决定步骤）。
• Decomposition of amino diazeniumdiolates (NONOates): Molecular mechanisms
  作者：Nizamuddin Shaikh、Marat Valiev、Sergei V. Lymar

  DOI：10.1016/j.jinorgbio.2014.08.008

  日期：2014.12

  Although diazeniumdiolates (X[N(O)NO](-)) are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release NO and/or its congeneric nitroxyl, the mechanisms of these processes remain obscure. In this work, we used a combination of spectroscopic, kinetic, and computational techniques to arrive at a quantitatively consistent molecular mechanism for decomposition of amino diazeniumdiolates (amino NONOates: R2N[N(O)NO](-), where R=N(C2H5)2 (1), N(C3H4NH2)2 (2), or N(C2H4NH2)2 (3)). Decomposition of these NONOates is triggered by protonation of their [NN(O)NO](-) group with the apparent pKa and decomposition rate constants of 4.6 and 1 s(-1) for 1; 3.5 and 0.083 s(-1) for 2; and 3.8 and 0.0033 s(-1) for 3. Although protonation occurs mainly on the O atoms of the functional group, only the minor R2N(H)N(O)NO tautomer (population ~10(-7), for 1) undergoes the NN heterolytic bond cleavage (kd~10(7) s(-1) for 1) leading to amine and NO. Decompositions of protonated amino NONOates are strongly temperature-dependent; activation enthalpies are 20.4 and 19.4 kcal/mol for 1 and 2, respectively, which includes contributions from both the tautomerization and bond cleavage. The bond cleavage rates exhibit exceptional sensitivity to the nature of R substituents which strongly modulate activation entropy. At pH<2, decompositions of all three NONOates that have been investigated are subject to additional acid catalysis that occurs through di-protonation of the [NN(O)NO](-) group.
• Nitroxylcob(III)alamin: Synthesis and X-ray Structural Characterization
  作者：Luciana Hannibal、Clyde A. Smith、Donald W. Jacobsen、Nicola E. Brasch

  DOI：10.1002/anie.200701131

  日期：2007.7.2
• Synthesis and Chemical and Biological Comparison of Nitroxyl- and Nitric Oxide-Releasing Diazeniumdiolate-Based Aspirin Derivatives
  作者：Debashree Basudhar、Gaurav Bharadwaj、Robert Y. Cheng、Sarthak Jain、Sa Shi、Julie L. Heinecke、Ryan J. Holland、Lisa A. Ridnour、Viviane M. Caceres、Regina C. Spadari-Bratfisch、Nazareno Paolocci、Carlos A. Velázquez-Martínez、David A. Wink、Katrina M. Miranda

  DOI：10.1021/jm400196q

  日期：2013.10.24

  Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.
• Anti-CD24 Antibody–Nitric Oxide Conjugate Selectively and Potently Suppresses Hepatic Carcinoma
  作者：Fumou Sun、Yang Wang、Xiaojun Luo、Zhaoxiong Ma、Yao Xu、Xinrong Zhang、Tian Lv、Yihua Zhang、Min Wang、Zhangjian Huang、Juan Zhang

  DOI：10.1158/0008-5472.can-18-2839

  日期：2019.7.1

  Nitric oxide (NO) has a wide range of potential applications in tumor therapy. However, a targeted delivery system for NO donors has remained elusive, creating a bottleneck that limits its druggability. The antibody–drug conjugate (ADC) is a targeted drug delivery system composed of an antibody linked to an active cytotoxic drug. This design may compensate for the weak targeting ability and various

  一氧化氮（NO）在肿瘤治疗中具有广泛的潜在应用。但是，针对NO供体的靶向递送系统仍然难以捉摸，从而形成了限制其可药物性的瓶颈。抗体-药物偶联物（ADC）是一种靶向药物递送系统，由与活性细胞毒性药物连接的抗体组成。该设计可以补偿NO供体的弱靶向能力和各种生物学功能。在这项研究中，我们设计了NO供体HL-2，它具有靶向的，裂解的二硫键和可连接的马来酰亚胺末端。我们将HL-2与通过硫醚键靶向CD24的抗体缀合，以生成ADC样的免疫缀合物，抗体-一氧化氮缀合物（ANC），我们将其命名为HN-01。HN-01表现出有效的内化作用，并显着增加了体外肝癌细胞中NO的释放。HN-01通过抗体依赖性共同毒性诱导荷肝癌裸鼠的肿瘤细胞凋亡并抑制肿瘤生长；HN-01还增加了肿瘤细胞中的NO水平。总的来说，这项研究扩展了ADC的概念，并提供了创新的NO供体和ANC，以解决NO定向输送中的当前挑战。ANC设计的这一新