精胺氮氧化加合物 | 136587-13-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 精胺氮氧化加合物
• 英文名称: Spermine nitric oxide complex
• 英文别名: (Z)-1-[N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino]diazen-1-ium-1,2-diolate；N-[4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl]-1,3-propanediamine；spermine NONOate；spermine-NONOate；SPER/NO；spermineNONOate；N-[3-aminopropyl-[4-(3-aminopropylamino)butyl]amino]-N-hydroxynitrous amide
• CAS: 136587-13-8
• 化学式: C₁₀H₂₆N₆O₂
• 分子量: 262.355
• InChiKey: QPIOUFBAROSIAN-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107°C
• 沸点：
  405.6°C (rough estimate)
• 密度：
  1.0879 (rough estimate)
• 溶解度：
  溶于甲醇，≥1mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -0.36
• 重原子数：
  18.0
• 可旋转键数：
  13.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  120.21
• 氢给体数：
  4.0
• 氢受体数：
  7.0

安全信息

• 海关编码：
  2928000090
• 储存条件：
  密封保存，并在-20°C下存放。

制备方法与用途

生物活性

Spermine NONOate 是一种一氧化氮 (NO) 与精胺的复合物，作为 NO 的供体，并可用于 NO 的制备。

体外研究

Spermine NONOate 在 37°C 下的半衰期为 39 分钟，在 22-25°C 下的半衰期为 230 分钟。

反应信息

• 作为反应物：
  描述：

  glutathion 、 精胺氮氧化加合物 在 Cu,Zn-superoxide dismutase 、 copper(II) sulfate 、 三乙胺 、 magnesium chloride 作用下， 生成 N-(N-L-γ-谷氨酰基-S-亚硝基-L-半胱氨酰----甘氨酸
  参考文献：
  名称：

  Aerobic nitric oxide-induced thiol nitrosation in the presence and absence of magnesium cations

  摘要：

  Although different routes for the S-nitrosation of cysteinyl residues have been proposed, the main in vivo pathway is unknown. We recently demonstrated that direct (as opposed to autoxidation-mediated) aerobic nitrosation of glutathione is surprisingly efficient, especially in the presence of Mg2+. In the present study we investigated this reaction in greater detail. From the rates of NO decay and the yields of nitrosoglutathione (GSNO) we estimated values for the apparent rate constants of 8.9 +/- 0.4 and 0.55 +/- 0.06 M-1 s(-1) in the presence and absence of Mg2+. The maximum yield of GSNO was close to 100% in the presence of Mg2+ but only about half as high in its absence. From this observation we conclude that, in the absence of Mg2+, nitrosation starts by formation of a complex between NO and O-2, which then reacts with the thiol. Omission of superoxide dismutase (SOD) reduced by half the GSNO yield in the absence of Mg2+, demonstrating O-2(-) formation. The reaction in the presence of Mg2+ seems to involve formation of a Mg2+.glutathione (GSH) complex. SOD did not affect Mg2+-stimulated nitrosation, suggesting that no O-2(-) is formed in that reaction. Replacing GSH with other thiols revealed that reaction rates increased with the pK(a) of the thiol, suggesting that the nucleophilicity of the thiol is crucial for the reaction, but that the thiol need not be deprotonated. We propose that in cells Mg2+-stimulated NO/O-2-induced nitrosothiol formation may be a physiologically relevant reaction. (C) 2014 The Authors. Published by Elsevier Inc.

  DOI：

  10.1016/j.freeradbiomed.2014.08.024
• 作为产物：
  描述：

  精胺 在 氧化亚氮 作用下， 以 四氢呋喃 为溶剂， 反应 120.0h， 以35%的产率得到精胺氮氧化加合物
  参考文献：
  名称：

  Complexes of ^.NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects

  摘要：

  Selected nucleophile/nitric oxide adducts [compounds which contain the anionic moiety, XN(O-)N = O] were studied for their ability to release nitric oxide spontaneously in aqueous solution and for possible vasoactivity. The diversity of structures chosen included those in which the nucleophile residue, X, was that of a secondary amine [Et2N, as in [Et2NN(N = O)O]Na, 1], a primary amine [iPrHN, as in [iPrHNN(N = O)O]Na, 2], a polyamine, spermine [as in the zwitterion H2N(CH2)3NH2+(CH2)4N[N(N = O)O-](CH2)3NH2, 3], oxide [as in Na[ON(N = O)O]Na, 4], and sulfite [as in NH4[O3SN(N = O)O]NH4, 5]. The rate constants (k) for decomposition in pH 7.4 phosphate buffer at 37-degrees-C, as measured by following loss of chromophore at 230-260 nm, were as follows: 1, 5.4 x 10(-3) s-1; 2, 5.1 X 10(-3) s-1; 3, 0.30 x 10(-3) s-1; 4, 5.0 x 10(-3) s-1; and 5, 1.7 x 10(-3) s-1. The corresponding extents of nitric oxide release (E(NO)) were 1.5, 0.73, 1.9, 0.54, and 0.001 mol/mol of starting material consumed, respectively, as determined from the integrated chemiluminescence response. Vasodilatory activities expressed as the concentrations required to induce 50% relaxation in norepinephrine-constricted aortic rings bathed in pH 7.4 buffer at 37-degrees-C (EC50) were as follows: 1, 0.19-mu-M; 2, 0.45-mu-M; 3, 6.2-mu-M; 4, 0.59-mu-M; and 5, 62-mu-M. Vasorelaxant potency (expressed as 1/EC50) was strongly correlated with the quantity of .NO calculated from the physicochemical data to be released in the interval required to achieve maximum relaxation at the EC50 doses (r = 0.995). This suggests that such nucleophile/.NO adducts might generally be useful as vehicles for the nonenzymatic generation of nitric oxide, in predictable amounts and at predictable rates, for biological purposes. The particular significance for possible drug design is underscored in the very favorable potency comparison between several of these agents and the established nitrovasodilators sodium nitroprusside and glyceryl trinitrate (EC50 values of 2.0 and > 10-mu-M, respectively) in parallel aortic ring tests.

  DOI：

  10.1021/jm00115a013
• 作为试剂：
  描述：

  L-酪氨酸 在 SOTS-1 、 精胺氮氧化加合物 作用下， 以 various solvent(s) 为溶剂， 反应 4.5h， 生成 3-硝基-L-酪氨酸 、 二酪氨酸
  参考文献：
  名称：

  一种以任何选定的摩尔比从化学来源就地生成一氧化氮和超氧化物的新颖方法。首次应用：酪氨酸氧化并与预先形成的过氧亚硝酸盐进行比较。

  摘要：

  已开发出以任何已知的恒定比率生成（*）NO和O（2）（*）（-）的第一种方法。在37摄氏度和pH值为7.5的条件下，精胺NONOate和二（4-羧基苄基）亚硝酸盐以一阶动力学和完全恒定的速率常数（80分钟的半衰期）衰减，得到200和40 mol％（*）的NO和O（ 2）（*）（-）。酪氨酸氧化成二氢酪氨酸和3-硝基酪氨酸（在这些实验中使用的主要和次要产物）（主要在CO（2）存在下）已使用（*）NO生成速率的不同比率进行了研究和O（2）（*）（-）。（*）NO / O（2）（*）（-）= 1.0的产品特征与从等量的（*）NO和O（2）（*）（-）产生的产品相似SIN-1的（*）NO / O（2）（*）（-）比率为1.0，但与从预制的过氧亚硝酸盐衍生的比率大不相同。所有的实验结果都可以用自由基化学来解释。可以令人满意地模拟所有（*）NO / O（2）（*）（-）比率下的产物谱，前提是要包括一组导致消耗二氢酪氨酸的重要反应。

  DOI：

  10.1021/tx0001272

文献信息

• Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions
  申请人：Kõster Hubert

  公开号：US20100248264A1

  公开（公告）日：2010-09-30

  Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

  提供了捕获化合物及其集合以及使用这些化合物进行生物分子分析的方法。特别地，提供了用于分析复杂蛋白质混合物（如蛋白质组）的集合、化合物和方法。这些化合物是多功能试剂，可用于分离和分离复杂的蛋白质混合物。还提供了执行这些方法的自动化系统。
• Use of nitric oxide mimetics in cancer treatment
  申请人：Cellegy Pharmaceuticals, Inc

  公开号：EP1502604A1

  公开（公告）日：2005-02-02

  Methods and formulations for inhibiting and preventing a malignant cell phenotype by administering to cells a low dose of a nitric oxide mimetic are provided

  提供了通过向细胞施用低剂量一氧化氮模拟物来抑制和预防恶性细胞表型的方法和制剂
• Nitric oxide donors in therapy of nitric oxide deficiency-induced disturbances of cerebral microcirculation
  申请人：Universitätsklinikum Münster

  公开号：EP2468269A1

  公开（公告）日：2012-06-27

  The present invention relates to nitric oxide releasing compounds and their use in the prevention, amelioration and/or therapy of nitric oxide (NO) deficiency induced disturbances of the cerebral microcirculation. The NO deficiency induced disturbances of the cerebral microcirculation may be due to an intracranial hemorrhage or stroke and can cause cerebrovascular spasms (or cerebral vasospasms) (CVS) and/or malperfusion of brain parenchyma caused by blood vessel and blood flow dysregulation which, in turn, can cause secondary neurological deficiencies (DIND) and/or brain infarction. Particularly, the present invention relates to the prevention, amelioration and/or therapy of delayed cerebral vasospasm-associated disorders after survived subarachnoidal hemorrhage by applying a NO-donor, most preferably Molsidomine.

  本发明涉及一氧化氮释放化合物及其在预防、改善和/或治疗一氧化氮（NO）缺乏引起的脑微循环障碍中的用途。一氧化氮缺乏引起的脑微循环障碍可能是由颅内出血或中风引起的，可导致脑血管痉挛（或脑血管痉挛）（CVS）和/或由血管和血流失调引起的脑实质灌注不良，进而导致继发性神经功能缺损（DIND）和/或脑梗塞。特别是，本发明涉及通过应用一种 NO 供体，最优选的是莫西多明，来预防、改善和/或治疗存活的蛛网膜下腔出血后迟发性脑血管痉挛相关疾病。
• MULTI-LAYER WOUND CARE PRODUCT WITH PERFORATED RELEASE LAYER
  申请人：BSN Medical GmbH

  公开号：EP3338813A1

  公开（公告）日：2018-06-27

  The invention relates to a multi-layered wound care product comprising multilayered wound care product comprising an upper liquid-absorbing layer an intermediate occlusive layer; and an active agent-releasing bottom layer wherein the last two layers have common pores or perforations that enable the passage of wound exudate through said two layers to reach the liquid-absorbing layer. The invention further relates to the use of said multi-layered wound care product for treatment of acute and chronic wounds. The invention finally relates to a method of producing the multi-layered wound care product of the invention.

  本发明涉及一种多层伤口护理产品，包括由上层液体吸收层、中间闭塞层和活性剂释放底层组成的多层伤口护理产品，其中后两层具有共同的孔隙或穿孔，使伤口渗出物能够通过所述两层到达液体吸收层。本发明还涉及使用所述多层伤口护理产品治疗急性和慢性伤口。本发明最后涉及一种生产本发明多层伤口护理产品的方法。
• Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype
  申请人：——

  公开号：US20020040059A1

  公开（公告）日：2002-04-04

  Methods and formulations for inhibiting and preventing a malignant cell phenotype by administering to cells a low dose of a nitric oxide mimetic are provided.

  本研究提供了通过向细胞施用低剂量一氧化氮模拟物来抑制和预防恶性细胞表型的方法和制剂。