6-甲氨基尿嘧啶 | 34284-87-2

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-甲氨基尿嘧啶
• 中文别名: 6-甲基氨基尿嘧啶
• 英文名称: 6-methylaminouracil
• 英文别名: 6-(methylamino)-1H-pyrimidine-2,4-dione
• CAS: 34284-87-2
• 化学式: C₅H₇N₃O₂
• mdl: MFCD01346696
• 分子量: 141.129
• InChiKey: ISUVRRPGXQIRDM-UHFFFAOYSA-N

物化性质

• 熔点：
  300-302℃
• 密度：
  1.36

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  70.2
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5-Amino-4-methylamino-uracil	80277-74-3	C5H8N4O2	156.144
  ——	5-bromo-6-methylamino-1H-pyrimidine-2,4-dione	98024-92-1	C5H6BrN3O2	220.026

反应信息

• 作为反应物：
  描述：

  6-甲氨基尿嘧啶 在 sodium hydroxide 、 sodium dithionite 、 溶剂黄146 、 sodium nitrite 作用下， 生成 5-Amino-4-methylamino-uracil
  参考文献：
  名称：

  Bredereck et al., Chemische Berichte, 1959, vol. 92, p. 583,594

  摘要：

  DOI：
• 作为产物：
  描述：

  9-甲基尿酸 在 乙二胺四乙酸 、 氧化亚氮 作用下， 以 phosphate buffer 为溶剂， 生成 6-甲氨基尿嘧啶
  参考文献：
  名称：

  Inactivation of Nitric Oxide by Uric Acid

  摘要：

  The 1980 identification of nitric oxide (NO) as an endothelial cell-derived relaxing factor resulted in an unprecedented biomedical research of NO and established NO as one of the most important cardiovascular, nervous and immune system regulatory molecule. A reduction in endothelial cell NO levels leading to endothelial dysfunction has been identified as a key pathogenic event preceding the development of hypertension, metabolic syndrome, and cardiovascular disease. The reduction in endothelial NO in cardiovascular disease has been attributed to the action of oxidants that either directly react with NO or uncouple its substrate enzyme. In this report, we demonstrate that uric acid (UA), the most abundant antioxidant in plasma, reacts directly with NO in a rapid irreversible reaction resulting in the formation of 6-aminouracil and depletion of NO. We further show that this reaction occurs preferentially with NO even in the presence of oxidants peroxynitrite and hydrogen peroxide and that the reaction is at least partially blocked by glutathione. This study shows a potential mechanism by which UA may deplete NO and cause endothelial dysfunction, particularly under conditions of oxidative stress in which UA is elevated and intracellular glutathione is depleted.

  DOI：

  10.1080/15257770802257952

文献信息

• Synthesis and Biological Evaluation of Novel Pyrimido[4,5-b]quinoline-2,4- dione Derivatives as MDM2 Ubiquitin Ligase Inhibitors
  作者：Xiaoxue Dou、Xin Li、Liu Tao、Chunqi Hu、Lei Zhang、Qiaojun He、Bo Yang、Yongzhou Hu

  DOI：10.2174/1573406411309040012

  日期：2013.4.1

  A series of pyrimido[4,5-b]quinoline-2,4-dione derivatives was synthesized and evaluated for their cytotoxic activities in vitro against five human cancer cell lines. Selected compounds were tested for their MDM2 E3 ligase inhibitory activities and p53-MDM2 binding inhibitory activities. Among tested compounds, four sulfur-containing compounds (4-7) displayed enhanced cytotoxic activities and better MDM2 E3 ligase inhibitoty activities in comparison with that of HLI98c. Three compounds (4-6) showed better p53-MDM2 binding inhibitory potency with IC50 values ranging from 1.3 μM to 9.0 μM.

  合成了一系列嘧啶并[4,5-b]喹啉-2,4-二酮衍生物，并在体外评估了它们对五种人类癌细胞株的细胞毒活性。对所选化合物的 MDM2 E3 连接酶抑制活性和 p53-MDM2 结合抑制活性进行了测试。在测试的化合物中，与 HLI98c 相比，四个含硫化合物（4-7）显示出更强的细胞毒性活性和更好的 MDM2 E3 连接酶抑制活性。三个化合物（4-6）显示出更好的 p53-MDM2 结合抑制效力，其 IC50 值从 1.3 μM 到 9.0 μM。
• Application of Chromatography. XXXI. Structure of a Green Fluorescent Substance produced by Eremothecium ashbyii.
  作者：Toru Masuda

  DOI：10.1248/cpb1953.5.28

  日期：——

  The green fluorescent substance (G compound) isolated from the mycelium of Ere-mothecium ashbyii was presumed to be a ribityl derivative of 6, 7-dimethyllumazine and already reported in the previous paper. In the present work 6, 7, 8-trimethyllumazine was synthesized, and from the complete agreement of ultraviolet spectrum between this product and G compound, the position of the ribityl group in G compound was confirmed to be the nitrogen at 8-position.

  上一篇论文中已经报道了从灰毛霉菌丝体中分离出的绿色荧光物质（G化合物），推测它是6，7-二甲基哒嗪的核糖基衍生物。本研究合成了 6，7，8-三甲基哒嗪，根据该产物与 G 化合物的紫外光谱完全一致，证实 G 化合物中的核糖基位置为 8 位上的氮。
• Toxoflavins and Deazaflavins as the First Reported Selective Small Molecule Inhibitors of Tyrosyl-DNA Phosphodiesterase II
  作者：Ali Raoof、Paul Depledge、Niall M. Hamilton、Nicola S. Hamilton、James R. Hitchin、Gemma V. Hopkins、Allan M. Jordan、Laura A. Maguire、Alison E. McGonagle、Daniel P. Mould、Mathew Rushbrooke、Helen F. Small、Kate M. Smith、Graeme J. Thomson、Fabrice Turlais、Ian D. Waddell、Bohdan Waszkowycz、Amanda J. Watson、Donald J. Ogilvie

  DOI：10.1021/jm400568p

  日期：2013.8.22

  The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAP.) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.
• 5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2
  作者：Michael P. Dickens、Patricia Roxburgh、Andreas Hock、Mokdad Mezna、Barrie Kellam、Karen H. Vousden、Peter M. Fischer

  DOI：10.1016/j.bmc.2013.09.038

  日期：2013.11

  Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e. g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
• Annulation of 6-aminouracils with 2,3-dimethoxy- and 2-fluorobenzaldehydes and 2-chloro-7-methoxyquinoline-3-carbaldehyde
  作者：R. G. Melik-Ohanjanyan、T. R. Hovsepyan、S. G. Israelyan、G. S. Karakhanyan、N. S. Minasyan

  DOI：10.1134/s1070428015100152

  日期：2015.10

  6-R-Aminouracils reacted with 2,3-dimethoxybenzaldehyde to give 10-R-substituted 9-methoxy-5-deazaflavins. No expected 5-deazaflavins were obtained in analogous reactions of 2,3-dimethoxybenzaldehyde with 6-aminouracil hydrochlorides. On the other hand, the corresponding 5-deazaflavin and naphthyridine hydrochlorides were formed in the reactions of 6-aminouracil hydrochlorides with 2-fluorobenzaldehyde and 2-chloro-7-methoxyquinoline-3-carbaldehyde. The newly synthesized 9,10-substituted 5-deazaflavins and benzo[b]pyrimido[5,4-g][1,8]naphthyridines attract interest as potential biologically active substances and substrates for further structural modifications.