6-氮杂胞苷 | 3131-60-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6-氮杂胞苷
• 英文名称: 6-azacytidine
• 英文别名: 2-(β-D-ribofuranosyl)-5-amino-1,2,4-triazin-3(2H)-one；5-amino-2-β-D-ribofuranosyl-2H-[1,2,4]triazin-3-one；6-aza cytidine；2-β-D-Ribofuranosyl-5-amino-1,2,4-triazin-3(2H)-on, 6-Aza-cytidin；6-Aza-cytidin；5-amino-2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazin-3-one
• CAS: 3131-60-0
• 化学式: C₈H₁₂N₄O₅
• 分子量: 244.207
• InChiKey: OZQDLJNDRVBCST-SHUUEZRQSA-N

物化性质

• 熔点：
  215 °C
• 沸点：
  387.12°C (rough estimate)
• 密度：
  1.4287 (rough estimate)
• 物理描述：
  6-azacytidine is a white crystalline powder. (NTP, 1992)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  6

制备方法与用途

类别：有毒物品

• 毒性分级：低毒
• 急性毒性：
  • 腹腔-大鼠 LD50: 9200 毫克/公斤
  • 腹腔-小鼠 LD50: 14000 毫克/公斤

可燃性危险特性：可燃；燃烧时会产生有毒的氮氧化物烟雾。

储运特性：库房需保持通风、低温和干燥环境。

灭火剂：使用干粉、泡沫、砂土、二氧化碳或雾状水。

反应信息

• 作为反应物：
  描述：

  6-氮杂胞苷 在 sodium periodate 、 sodium tetrahydroborate 作用下， 以92%的产率得到5-amino-2-[2-hydroxy-1'-(2''-hydroxy-1''-hydroxymethylethoxy)ethyl]-1,2,4-triazin-3(2H)-one
  参考文献：
  名称：

  Synthesis and Comparative Study of Anti-Adenoviral Activity of 6-Azacytidine and Its Analogues

  摘要：

  This paper presents the results of synthesis and study of cytotoxicity and the anti-adenoviral activity of new N4-derivatives of 6-azacytidine and its alpha-L-glycopyranosyl analogues obtained by the simplified one-pot version of the silyl condensation method. The resulting acylated 4-methylmercapto-1,2,4-triazin-3(2H)-one glycosides then underwent the amination and/or ammonolysis to provide 6-azacytidine glycoside analogues (2-6, 12, 15, 17) and compounds with modifications at both base and sugar fragments (11, 15). The evaluation of cytotoxicity and antiviral activity of new compounds against AdV5 showed high selectivity indexes for N4-methyl-6-azacytidine (2) and N,O-tetraacetyl-6-azacytidine (8). High anti-adenoviral activity of N4-methyl-6-azacytidine as well as very low cytotoxicity may suggest its further investigation as potential compound for the therapy of AdV infection.

  DOI：

  10.1080/15257770.2015.1034363
• 作为产物：
  描述：

  Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-oxo-5-[1,2,4]triazol-1-yl-3H-[1,2,4]triazin-2-yl)-tetrahydro-furan-3-yl ester 在 氨 、 氯化铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 吡啶 、 甲醇 为溶剂， 反应 48.0h， 生成 6-氮杂胞苷
  参考文献：
  名称：

  Biochemical Detection of Cytidine Protonation within RNA

  摘要：

  Perturbation of active site functional group pK(a)s is an important strategy employed by protein enzymes to achieve catalysis. There is increasing evidence to indicate that RNAs also utilize functional group pK(a) perturbation for folding and reactivity. one of the best candidates for a functionally relevant pK(a) perturbation is the N3 of C (pK(a) 4.2), which could be sufficiently raised to allow protonation near physiological pH. Here we report the synthesis and use of a series of alpha -phosphorothioate tagged cytidine analogues whose altered N3 pK(a)s make it possible to efficiently detect functionally relevant protonation events by nucleotide analogue interference mapping. 6-Azacytidine (n(6)C alphaS) and 5-fluorocytidine (f(5)C alphaS) both have enhanced acidity at the N3 position (pK(a) 2.6 and 2.3, respectively) but leave the hydrogen bonding face of C otherwise unaffected. In contrast, pseudoisocytidine (Psi iC alphaS) is a charge neutral analogue that mimics the hydrogen bonding character of protonated C. To test the utility of these analogues, we characterized the C300(+)-G97-C277 mutant form of the Tetrahymena group I intron, which is predicted to require C300 protonation for ribozyme folding and reactivity. At neutral to alkaline pHs, C300 was the only site of n(6)C alphaS and f(5)C alphaS interference within the intron, yet both interferences were rescued at acidic pH. Furthermore,Psi iC alphaS substitution at C300 resulted in enhanced activity at alkaline pHs, consistent with the presence of an N3 proton under the pH conditions studied. Interference mapping with these analogues provides an efficient and sensitive means to identify every site within an RNA where cytidine protonation is important for RNA function and may make it possible to identify C's that participate in general acid/base catalysis within ribozyme active sites.

  DOI：

  10.1021/ja001918t

文献信息

• [EN] COMPOSITIONS AND METHODS FOR SYNTHESIS OF PHOSPHORYLATED MOLECULES<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE SYNTHÈSE DE MOLÉCULES PHOSPHORYLÉES
  申请人：UNIV CALIFORNIA

  公开号：WO2019195494A1

  公开（公告）日：2019-10-10

  The invention provides compositions and methods for synthesis of phosphorylated organic compounds, including nucleoside triphosphates.

  这项发明提供了合成磷酸化有机化合物的组合物和方法，包括核苷三磷酸。
• [EN] NOVEL PHOSPHOROUS (V)-BASED REAGENTS, PROCESSES FOR THE PREPARATION THEREOF, AND THEIR USE IN MAKING STEREO-DEFINED ORGANOPHOSHOROUS (V) COMPOUNDS<br/>[FR] NOUVEAUX RÉACTIFS À BASE DE PHOSPHORE (V), LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION DANS LA FABRICATION DE COMPOSÉS ORGANOPHOSHOREUX (V) STÉRÉODÉFINIS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019200273A1

  公开（公告）日：2019-10-17

  The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.

  本发明涉及新型磷（V）（P(V)）试剂，其制备方法以及利用这种新型试剂制备有机磷（V）化合物的方法。
• Nucleotide mimics and their prodrugs
  申请人：——

  公开号：US20040059104A1

  公开（公告）日：2004-03-25

  The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

  本发明涉及核苷二磷酸模拟物和核苷三磷酸模拟物，其中包含二磷酸或三磷酸基团模拟物，以及可选的糖修饰和/或碱基修饰。本发明的核苷酸模拟物，以药学上可接受的盐、药学上可接受的前药或药物配方的形式，可用作抗病毒、抗微生物和抗癌剂。本发明提供了一种治疗病毒感染、微生物感染和增生性疾病的方法。本发明还涉及包含本发明化合物的药物组合物，可选地与其他药理活性剂结合。
• [EN] COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'ADMINISTRER DES AGENTS THÉRAPEUTIQUES
  申请人：MODERNATX INC

  公开号：WO2017099823A1

  公开（公告）日：2017-06-15

  This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

  这项披露提供了改进的基于脂质的组合物，包括脂质纳米粒子组合物，以及它们用于体内传递药剂的方法，包括核酸和蛋白质。这些组合物不受加速血清清除的影响，并且它们在体内具有改进的毒性特性。
• [EN] COMPOUNDS FOR THE REDUCTION OF THE DELETERIOUS ACTIVITY OF EXTENDED NUCLEOTIDE REPEAT CONTAINING GENES<br/>[FR] COMPOSÉS POUR LA RÉDUCTION DE L'ACTIVITÉ DÉLÉTÈRE DE GÈNES CONTENANT UNE RÉPÉTITION DE NUCLÉOTIDES ÉTENDUE
  申请人：NUREDIS INC

  公开号：WO2020131573A1

  公开（公告）日：2020-06-25

  Aspects of the present disclosure include methods of reducing the deleterious impact of a target gene in a cell, such as the deleterious activity of a mutant extended nucleotide repeat (NR) containing target gene in a cell by contacting the cell with an effective amount of a tetrahydrocarbazole compound. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended NR containing target gene may be reduced, e.g., by reducing (and in some instances differentially, including selectively, reducing) the production or activity of toxic expression products (e.g., RNA or protein) encoded by the target gene. Kits and compositions for practicing the subject methods are also provided.

  本公开内容的方面包括减少目标基因在细胞中的有害影响的方法，例如通过将细胞与有效量的四氢咔唑化合物接触，减少含有突变延伸核苷酸重复序列（NR）的目标基因在细胞中的有害活性。突变延伸NR包含的目标基因的有害活性（例如，由此编码的产物的毒性和/或功能障碍）可以减少，例如，通过减少（在某些情况下包括选择性地减少）由目标基因编码的有毒表达产物（例如，RNA或蛋白质）的生产或活性。还提供了用于实施所述方法的试剂盒和组合物。