N-[2-(5-甲氧基-1-亚硝基吲哚-3-基)乙基]乙酰胺 | 278783-22-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: N-[2-(5-甲氧基-1-亚硝基吲哚-3-基)乙基]乙酰胺
• 英文名称: N-[2-(5-methoxy-1-nitroso-1H-indol-3-yl)ethyl]acetamide
• 英文别名: N-nitrosomelatonin；Acetamide, N-[2-(5-methoxy-1-nitroso-1H-indol-3-yl)ethyl]-；N-[2-(5-methoxy-1-nitrosoindol-3-yl)ethyl]acetamide
• CAS: 278783-22-5
• 化学式: C₁₃H₁₅N₃O₃
• 分子量: 261.28
• InChiKey: AAFVLLXWXVZVJG-UHFFFAOYSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(5-甲氧基-1-亚硝基吲哚-3-基)乙基]乙酰胺 在 Tris-HCl buffer 、 L-半胱氨酸 作用下， 以 乙醇 、 水 为溶剂， 生成 褪黑素
  参考文献：
  名称：

  Mechanisms of NO Release by N¹-Nitrosomelatonin:  Nucleophilic Attack versus Reducing Pathways

  摘要：

  A new type of physiologically relevant nitrosamines have been recently recognized, the N-1-nitrosoindoles. The possible pathways by which N-1-nitrosomelatonin (NOMel) can react in physiological environments have been studied. Our results show that NOMel slowly decomposes spontaneously in aqueous solution, generating melatonin as the main organic product (k = (3.7 +/- 1.1) x 10(-5) s(-1), Tris-HCl (0.2 M) buffer, pH 7.4 at 37 degrees C, anaerobic). This rate is accelerated by acidification (k(pH) (5.8) = (4.5 +/- 0.7) x 10(-4) s(-1), k(pH 8.8) = (3.9 +/- 0.6) x 10(-6) s(-1), Tris-HCl (0.2 M) buffer at 37 degrees C), by the presence of O-2 (k(o) = (9.8 +/- 0.1) x 10(-5) s(-1), pH 7.4, 37 degrees C, [NOMel] = 0.1 mM, P(O-2) = 1 atm), and by the presence of the spin trap TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl; k(o) = (2.0 +/- 0.1) x 10(-4) s(-1), pH 7.4, 37 degrees C, [NOMel] = 0.1 mM, [TEMPO] = 9 mM). We also found that NOMel can transnitrosate to L-CySteinate, producing S-nitrosocysteine and melatonin (k(o) = 0.127 +/- 0.002 M-1 s-1, Tris-HCl (0.2 M) buffer, pH 7.4 at 37 T). The reaction of NOMel with ascorbic acid as a reducing agent has also been studied. This rapid reaction produces nitric oxide and melatonin. The saturation of the observed rate constant (k(o) = (1.08 +/- 0.04) x 10(-3) s(-1), Tris-HCl (0.2 M) buffer, pH 7.4 at 37 degrees C) at high ascorbic acid concentration (100-fold with respect to NOMel) and the pH independence of this reaction in the pH range 7-9 indicate that the reactive species are ascorbate and melatonyl radical originated from the reversible homolysis of NOMel. Taking into account kinetic and DFT calculation data, a comprehensive mechanism for the denitrosation of NOMel is proposed. On the basis of our kinetics results, we conclude that under physiological conditions NOMel mainly reacts with endogenous reducing agents (such as ascorbic acid), producing nitric oxide and melatonin.

  DOI：

  10.1021/jo047720z
• 作为产物：
  描述：

  褪黑素 在 盐酸 、 sodium nitrite 作用下， 以 水 、 丙酮 为溶剂， 生成 N-[2-(5-甲氧基-1-亚硝基吲哚-3-基)乙基]乙酰胺
  参考文献：
  名称：

  亚硝基二硫醇分解产物的形成取决于亚硝化程度。二亚硝基二硫苏糖醇仅充当释放一氧化氮的化合物的证据。

  摘要：

  迄今为止，尚未明确阐明亚硝化二硫醇的衰变机理以及相关产物的形成。在本文中，我们证明了亚硝化的dl-二硫苏糖醇（DTT）通过两条独立的途径衰减，即一条仅产生一氧化氮，另一条产生（最初）硝氧基（HNO / 3NO-）。两种分解途径的重要性取决于DTT的亚硝化程度。二亚硝基二硫苏糖醇（NODTTNO）定量生成一氧化氮，而一亚硝基二硫苏糖醇（NODTT）最初生成硝氧基。由于NODTT和DTT都是硝氧基的目标，因此它们的可用性决定了HNO衍生的一氧化氮（以NODTT为反应物）或羟胺和铵离子（以DTT为反应物）的形成。由HNO-DTT反应形成的NH4 +可能是通过不依赖NH2OH的逐步机理进行的，因为通过N-15 NMR光谱鉴定出DTT衍生的亚磺酰胺为中间体。我们的数据符合以下假设：三重态硝酰基（3NO-）是由NODTT的去质子化（硫醇盐）形式的单分子衰减形成的，因为CBS-QB3计算预测了后者的低价

  DOI：

  10.1039/b801583j

文献信息

• [EN] ARYL IMIDAZOLE COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉ ARYLIMIDAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA PROTÉINE AMYLOÏDE BÊTA
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098488A1

  公开（公告）日：2010-09-02

  A compound represented by the formula (I): or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a triazolyl group or the like which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物，或其药理学上可接受的盐或酯，其中环A代表可能被取代的三唑基团或类似物，环B代表可能被取代的苯基团或类似物，X1代表单键或类似物，R1和R2分别代表C1-6烷基或类似物，m代表0到3的整数，n代表0到2的整数，对于由Aβ引起的疾病具有治疗作用。
• MULTI-CYCLIC COMPOUNDS
  申请人：KIMURA Teiji

  公开号：US20090062529A1

  公开（公告）日：2009-03-05

  A compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar 1 represents an imidazolyl group or the like which may be substituted with a C1-6 alkyl group, Ar 2 represents a phenyl group or the like which may be substituted with a C1-6 alkoxy group, X 1 represents a double bond or the like and Het represents a triazolyl group or the like which may be substituted with a C1-6 alkyl group or the like, is effective as a therapeutic or prophylactic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物或其药理学可接受的盐，其中Ar1代表可用C1-6烷基基团取代的咪唑基团或类似基团，Ar2代表可用C1-6烷氧基团取代的苯基团或类似基团，X1代表双键或类似基团，Het代表可用C1-6烷基基团或类似基团取代的三唑基团或类似基团，对由Aβ引起的疾病具有治疗或预防作用。
• [EN] NITROGEN-CONTAINING FUSED HETEROCYCLIC COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS CONTENANT DE L'AZOTE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA BÊTA-AMYLOÏDE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098487A1

  公开（公告）日：2010-09-02

  A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a five-membered aromatic heterocyclic group or the like fused with a non-aromatic ring group, which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  化合物的分子式为[I]：或其药理学可接受的盐或酯，其中环A代表一个五元芳香杂环基团或类似于非芳香环基团的融合物，可以被取代，环B代表一个苯基或类似的基团，可以被取代，X1代表一个单键或类似物，R1和R2分别代表一个C1-6烷基基团或类似物，m表示0到3的整数，n表示0到2的整数，对由Aβ引起的疾病具有治疗作用。
• A Surface Effect Allows HNO/NO Discrimination by a Cobalt Porphyrin Bound to Gold
  作者：Sebastián A. Suárez、Mariano H. Fonticelli、Aldo A. Rubert、Ezequiel de la Llave、Damián Scherlis、Roberto C. Salvarezza、Marcelo A. Martí、Fabio Doctorovich

  DOI：10.1021/ic1007022

  日期：2010.8.2

  Nitroxyl (HNO) is a small short-lived molecule for which it has been suggested that it could be produced, under certain cofactors conditions, by nitric oxide (NO) synthases. Biologically relevant targets of HNO are heme proteins, thiols, molecular oxygen, NO, and HNO itself. Given the overlap of the targets and reactivity between NO and HNO, it is very difficult to discriminate their physiopathological

  硝基氧（HNO）是一个短寿命的小分子，已经有人提出在某些辅助因子条件下可以通过一氧化氮（NO）合成酶生产硝基氧。HNO的生物学相关靶标是血红素蛋白，硫醇，分子氧，NO和HNO本身。考虑到靶标的重叠和NO与HNO之间的反应性，很难完全地区分它们的生理病理学作用，并且它们之间的准确区分仍然是解释该领域正在进行的研究的关键。钴（II）卟啉对NO的高反应性和稳定性以及通过S-Au键将卟啉与电极共价结合的简便有效方式促使我们测试了钴（II​​）5,10,15,20-四[3-] （p-乙酰硫代丙氧基）苯基]卟啉[Co（P）]，可能是对两种物质进行电化学鉴别的可能方法。为此，首先，我们研究了NO，NO供体和常用的HNO供体与Co II（P）和Co III（P）之间的反应。其次，我们将Co II（P）共价连接到金电极上，并通过电化学技术以及扫描隧道显微镜，X射线光电子能谱和固态密度泛函理论计算来表征其氧化
• [EN] IMIDAZOLYLPYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLYLPYRAZINE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098495A1

  公开（公告）日：2010-09-02

  To provide a novel low-molecular-weight compound that inhibits the production of amyloid-β (Aβ ). A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein R1 and R2 are the same or different and each represent a substituent selected from the following Substituent Group a1; m represents an integer of 0 to 3; n represents an integer of 0 to 2; X1 represents a single bond or the like; X2 represents a single bond or the like; Ring A represents a five-membered aromatic heterocyclic group or the like which contains two or more nitrogen atoms and may have 1 to 3 substituents selected from the following Substituent Group b1; and Ring B represents a monocyclic or fused cyclic aromatic ring group such as the formula [2] which may have 1 to 3 substituents selected from the following Substituent Group c1, is effective as a therapeutic agent for a disease such as Alzheimer's disease. Substituent Group a1: a C1-6 alkyl group and the like Substituent Group b1: a C1-6 alkyl group and the like Substituent Group c1: an amino group and the like

  提供一种新型低分子量化合物，该化合物能够抑制淀粉样蛋白-β（Aβ）的产生。表示为化学式[I]的化合物，或其药理学上可接受的盐或酯，其中R1和R2相同或不同，每个代表以下取代基团a1中选择的取代基；m代表0到3的整数；n代表0到2的整数；X1代表单键或类似物；X2代表单键或类似物；环A代表含有两个或更多氮原子并且可能具有1到3个取代基团b1中选择的取代基的五元芳香杂环基团或类似物；环B代表可能具有1到3个取代基团c1中选择的取代基的单环或融合环芳香环基团，如化学式[2]所示，对于阿尔茨海默病等疾病具有治疗作用。取代基团a1：C1-6烷基基团等；取代基团b1：C1-6烷基基团等；取代基团c1：氨基团等。