6-羟基l氨基尿嘧啶 | 20555-88-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 6-羟基l氨基尿嘧啶
• 英文名称: N⁴-hydroxycytosine
• 英文别名: N⁴-Hydroxy-cytosin；1H-pyrimidine-2,4-dione 4-oxime；4-hydroxyamino-1H-pyrimidin-2-one；6-(hydroxyamino)-1H-pyrimidin-2-one
• CAS: 20555-88-8
• 化学式: C₄H₅N₃O₂
• mdl: MFCD00463651
• 分子量: 127.103
• InChiKey: OSHIQPFXKULOPB-UHFFFAOYSA-N

物化性质

• 熔点：
  >270°C (dec.)
• 密度：
  1.65±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.7
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090
• 包装等级：
  III
• 危险类别：
  4.1
• 危险性防范说明：
  P240,P210,P241,P264,P280,P302+P352,P370+P378,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险品运输编号：
  1325
• 危险性描述：
  H315,H319,H228
• 储存条件：
  存储条件为：2-8°C，避光，惰性气体环境中。

制备方法与用途

n-羟基胞嘧啶是一种非常有用的研究化学物质。

反应信息

• 作为反应物：
  描述：

  6-羟基l氨基尿嘧啶 在 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.38h， 生成 胞嘧啶
  参考文献：
  名称：

  The Mitochondrial Amidoxime Reducing Component (mARC) Is Involved in Detoxification of N-Hydroxylated Base Analogues

  摘要：

  The "mitochondrial Amidoxime Reducing Component" (mARC) is the newly discovered fourth molybdenum enzyme in mammals. All hitherto analyzed mammals express two mARC proteins, referred to as mARC1 and mARC2. Together with their electron transport proteins cytochrome b(5) and NADH cytochrome b(5) reductase, they form a three-component enzyme system and catalyze the reduction of N-hydroxylated prodrugs. Here, we demonstrate the reductive detoxification of toxic and mutagenic N-hydroxylated nucleobases and their corresponding nucleosides by the mammalian mARC-containing enzyme system. The N-reductive activity was found in all tested tissues with the highest detectable conversion rates in liver, kidney, thyroid, and pancreas. According to the presumed localization, the N-reductive activity is most pronounced in enriched mitochondrial fractions. In vitro assays with the respective recombinant three-component enzyme system show that both mARC isoforms are able to reduce N-hydroxylated base analogues, with mARC1 representing the more efficient isoform. On the basis of the high specific activities with N-hydroxylated base analogues relative to other N-hydroxylated substrates, our data suggest that mARC proteins might be involved in protecting cellular DNA from misincorporation of toxic N-hydroxylated base analogues during replication by converting them to the correct purine or pyrimidine bases, respectively.

  DOI：

  10.1021/tx300298m
• 作为产物：
  描述：

  胞嘧啶 在 硫酸羟胺 、 sodium methylate 作用下， 以 乙醇 、 水 为溶剂， 以93.7%的产率得到6-羟基l氨基尿嘧啶
  参考文献：
  名称：

  N4-羟基胞苷的制备方法

  摘要：

  本发明揭示了一种具有预防和治疗包括新冠(COVID‑19)在内的多种病毒感染作用的N4‑羟基胞苷的制备方法，其制备步骤包括：以胞嘧啶和四乙酰核糖为起始原料，经羟胺化、缩合和水解反应制得N4‑羟基胞苷。该制备方法原料易得，工艺简洁，经济环保，适合工业化生产。

  公开号：

  CN113307833B

文献信息

• Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity
  作者：Steffi Noll、Marijeta Kralj、Lidija Šuman、Holger Stephan、Ivo Piantanida

  DOI：10.1016/j.ejmech.2008.06.002

  日期：2009.3

  The antiproliferative activity screening on human tumor cell lines of a series of modified uracil and cytosine bases as well as some corresponding acyclonucleosides, and comparison of structure–activity relationship revealed the importance of chemical reactivity of the substituent attached to the C5-position of uracil for the activity of studied compounds. Namely, the results obtained for the most

  一系列修饰的尿嘧啶和胞嘧啶碱基以及一些相应的无环核苷在人肿瘤细胞系中的抗增殖活性筛选，以及结构-活性关系的比较表明，尿嘧啶C5位上取代基的化学反应活性对于研究化合物的活性。即，对于活性最高的化合物5-（氯乙酰氨基）尿嘧啶（2）及其无环糖类似物18所获得的结果表明，反应性取代基与胸苷酸合酶机制内若干可能的靶标之间形成了共价键（半胱氨酸残基，酶的基本部分，N，N-亚甲基四氢叶酸或其反应性亚胺形式）是最可能的作用方式。另外，新型的C 5-取代的尿嘧啶衍生物6（5- [双-（2-对-甲氧基苄基硫乙基）胺]乙酰氨基尿嘧啶）通过未知的机制对HeLa和MiaPaCa-2细胞系表现出高的抗增殖活性。
• 5’-异丁酰基-N4-羟基胞苷的制备方法
  申请人：苏州立新制药有限公司

  公开号：CN113278040B

  公开（公告）日：2022-07-05

  本发明揭示了一种具有预防和治疗包括新冠(COVID‑19)在内的多种病毒感染作用的5’‑异丁酰基‑N4‑羟基胞苷的制备方法，其制备步骤包括：以D‑核糖和胞嘧啶为起始原料，分别通过叉丙酮保护、酰化和羟胺化反应，所得化合物经过缩合和水解反应制得式I化合物5’‑异丁酰基‑N4‑羟基胞苷。该制备方法原料易得，工艺简洁，经济环保，适合工业化生产。
• Atkins, Paul J.; Palling, David J.; Poon, Nai L., Journal of the Chemical Society. Perkin transactions II, 1982, p. 1107 - 1112
  作者：Atkins, Paul J.、Palling, David J.、Poon, Nai L.、Hall, C. Dennis

  DOI：——

  日期：——
• Palling, David J.; Schalke, Peter M.; Atkins, Paul J., Journal of the Chemical Society. Perkin transactions II, 1981, p. 113 - 120
  作者：Palling, David J.、Schalke, Peter M.、Atkins, Paul J.、Hall, C. Dennis

  DOI：——

  日期：——
• The Mitochondrial Amidoxime Reducing Component (mARC) Is Involved in Detoxification of N-Hydroxylated Base Analogues
  作者：Nina Krompholz、Carmen Krischkowski、Debora Reichmann、Dieter Garbe-Schönberg、Ralf-R. Mendel、Florian Bittner、Bernd Clement、Antje Havemeyer

  DOI：10.1021/tx300298m

  日期：2012.11.19

  The "mitochondrial Amidoxime Reducing Component" (mARC) is the newly discovered fourth molybdenum enzyme in mammals. All hitherto analyzed mammals express two mARC proteins, referred to as mARC1 and mARC2. Together with their electron transport proteins cytochrome b(5) and NADH cytochrome b(5) reductase, they form a three-component enzyme system and catalyze the reduction of N-hydroxylated prodrugs. Here, we demonstrate the reductive detoxification of toxic and mutagenic N-hydroxylated nucleobases and their corresponding nucleosides by the mammalian mARC-containing enzyme system. The N-reductive activity was found in all tested tissues with the highest detectable conversion rates in liver, kidney, thyroid, and pancreas. According to the presumed localization, the N-reductive activity is most pronounced in enriched mitochondrial fractions. In vitro assays with the respective recombinant three-component enzyme system show that both mARC isoforms are able to reduce N-hydroxylated base analogues, with mARC1 representing the more efficient isoform. On the basis of the high specific activities with N-hydroxylated base analogues relative to other N-hydroxylated substrates, our data suggest that mARC proteins might be involved in protecting cellular DNA from misincorporation of toxic N-hydroxylated base analogues during replication by converting them to the correct purine or pyrimidine bases, respectively.