N¹-methyl-2'-deoxyguanosine | 5132-79-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N¹-methyl-2'-deoxyguanosine
• 英文别名: 1-N-methyl-2'-deoxyguanosine；1-methyl-2'-deoxyguanosine；2'-deoxy-1-methylguanosine；1-methyldeoxyguanosine；N¹-Me-dGuo；1-methyl-2'-deoxy-guanosine；N1-Methyl-2'-deoxyguanosine；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1-methylpurin-6-one
• CAS: 5132-79-6
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: VJSHSPNFYFRXGN-RRKCRQDMSA-N

物化性质

• 熔点：
  >227°C (dec.)
• 沸点：
  690.7±65.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、加热）、水（轻微、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 储存条件：
  2-8°C

制备方法与用途

2'-脱氧-N1-甲基鸟苷是一种嘌呤核苷类似物，具有广泛抗肿瘤活性，主要用于治疗惰性淋巴系统恶性肿瘤。其抗癌机制主要通过抑制DNA合成和诱导细胞凋亡来实现。

反应信息

• 作为反应物：
  描述：

  N¹-methyl-2'-deoxyguanosine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 水 为溶剂， 以71%的产率得到8-bromo-1-methyl-2'-deoxyguanosine
  参考文献：
  名称：

  Inhibitory Effects of the Guanine Moiety on Suzuki Couplings of Unprotected Halonucleosides in Aqueous Media

  摘要：

  In the Suzuki arylations of unprotected halonucleosides in aqueous media, 8-bromo-2'-deoxyguanosine (8BrdG) couplings were slower to reach completion than the corresponding 8-bromo-2'deoxyadenosine (8BrdA) couplings. The guanine moiety has an acidic proton, which under our Suzuki conditions (PH congruent to 10) may be deprotonated to give an anion that can coordinate to palladium. The possibility that guanine coordination was responsible for the observed slower rates was explored using additive experiments in which nonhalogenated nucleosides were added to the Suzuki coupling reaction of 8BrdA or 4-bromotoluene and PhB(OH)(2) and the reaction progress monitored by HPLC or GC. Adding dG slowed these reactions, and an induction period was observed. The addition of dA or 1-methyl-2'-deoxyguanosine (lMedG) to these couplings did not affect the rate of conversion to product. Guanine coordination was further explored using C-13 and P-31 NMR spectroscopy, which implies that guanine is coordinating to palladium through N-1 or O-6, or both. Furthermore, the presence of dG inhibited the formation of the active palladium(0) catalytic species, which may account for both the observed induction period and the sluggishness of reactions where guanine is involved.

  DOI：

  10.1021/jo050832l
• 作为产物：
  描述：

  3',5'-di-O-acetyl-2'-deoxy-N2-[(dimethylamino)methylene]-1-methylguanosine 在 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 96.0h， 以80%的产率得到N¹-methyl-2'-deoxyguanosine
  参考文献：
  名称：

  核苷酸。第LXXVIII部分

  摘要：

  几个Ñ（羟基烷基）-2,4-二硝基苯胺转化成它们的亚磷酰胺（参见5和6在方案1）鉴于它们作为荧光猝灭剂的使用，和改性的2-氨基苯甲酰胺（参见图9，10，18，和19在方案1中）在模型反应施加为荧光团，以确定3'-ABA的相对荧光量子产率和5'-DNP-3'-ABA共轭物（ABA =氨基苯甲酰胺，DNP =二硝基苯胺）。胸苷用N-（2-氯乙基）-2-，4-二硝基苯胺（24）烷基化，得到25，然后将其进一步修饰为结构单元27和28（方案3）。29中的2-氨基通过重氮化转化为2-氟肌苷衍生物30，用作在嘧啶核上进行数个反应的起始原料（→ 31、33和35；方案4）。3'，5'-二-O-乙酰基-2'-脱氧-N 2 -[（（二甲基氨基）亚甲基]鸟苷（37）被甲基和乙基碘化物优先在N（1）分别烷基化至43和44，并且类似地反应ñ - （2-氯乙基）-2,4-二硝基苯胺（24），以38和N-（2-碘乙基

  DOI：

  10.1002/hlca.201000253

文献信息

• [EN] MODIFIED NUCLEOSIDES<br/>[FR] NUCLÉOSIDES MODIFIÉS
  申请人：UNIV KONSTANZ

  公开号：WO2017097973A1

  公开（公告）日：2017-06-15

  The present invention relates to modified nucleosides which are linked to cargo molecules and which can be incorporated by DNA or RNA polymerases in strand synthesis. The present invention also relates to use of such modified nucleosides as substrates for DNA or RNA polymerases. The present invention also relates to the use of such modified nucleosides in diagnosis and prognosis of diseases or disorders associated with a target sequence. The present invention also relates to methods for producing such modified nucleosides, kits comprising such nucleosides, and in vitro methods for diagnosing or predicting diseases or disorders associated with a target sequence. The present invention also relates to modified nucleosides for use in diagnosing, predicting or treating diseases or disorders associated with a target sequence.

  本发明涉及与载荷分子连接的修饰核苷，可以由DNA或RNA聚合酶在链合成中合并。本发明还涉及将这种修饰核苷用作DNA或RNA聚合酶的底物的用途。本发明还涉及将这种修饰核苷用于诊断和预测与靶序列相关的疾病或紊乱的用途。本发明还涉及生产这种修饰核苷的方法，包括这种核苷的试剂盒，以及用于诊断或预测与靶序列相关的疾病或紊乱的体外方法。本发明还涉及用于诊断、预测或治疗与靶序列相关的疾病或紊乱的修饰核苷。
• OLIGODEOXYRIBONUCLEOTIDES
  申请人：Shudo, Koichi, Prof. Dr.

  公开号：EP0540742A1

  公开（公告）日：1993-05-12

  An oligodeoxynucleotide including an oligonucleotide comprising 5' - phosphates of a nucleoside, formed by combining 2 - deoxy - L - erythro- pentose with a nucleic acid base in the form of a β- anomer, linked with each other through 3'-5' phosphodiester linkages; and another oligodeoxynucleotide including an oligonucleotide comprising 5'-phosphates of a nucleoside, formed by combining 2 - deoxy - D - ribose with a nucleic acid base in the form of a β- anomer, and 5' - phosphates of another nucleoside, formed by combining 2 - deoxy - L - erythro- pentose with a nucleic acid base in the form of a β- anomer, linked with each other alternatingly through 3'-5' phosphodiester linkages. Each of the oligodeoxynucleotides combines specifically with a natural oligonucleotide having a complementary base sequence and is useful as an antisense DNA having an activity of inhibiting gene expression. These oligodeoxynucleotides can be efficiently produced by the solid phase method using a phosphoramidite derivative containing a 2-deoxy-β- L-erythro-pentofuranosyl moiety.

  一种寡核苷酸，包括包含5'-核苷酸磷酸的寡核苷酸，由将2'-去氧-L-赤霉糖与以β-异构体形式的核酸碱基结合而成，通过3'-5'磷酸二酯键连接在一起；另一种寡核苷酸，包括包含5'-核苷酸磷酸的寡核苷酸，由将2'-去氧-D-核糖与以β-异构体形式的核酸碱基结合而成，并且由将2'-去氧-L-赤霉糖与以β-异构体形式的核酸碱基结合而成的另一个核苷酸磷酸连接在一起，通过3'-5'磷酸二酯键交替连接在一起。这些寡核苷酸分别与具有互补碱基序列的天然寡核苷酸特异结合，并可用作具有抑制基因表达活性的反义DNA。这些寡核苷酸可以通过使用含有2'-去氧-β-L-赤霉糖基团的磷酰胺酰胺衍生物的固相法高效制备。
• Chemical Properties of Oxopropenyl Adducts of Purine and Pyrimidine Nucleosides and Their Reactivity toward Amino Acid Cross-Link Formation
  作者：Joseph Szekely、Carmelo J. Rizzo、Lawrence J. Marnett

  DOI：10.1021/ja074506u

  日期：2008.2.1

  of 8.2. Cross-linking of 2, 4, 5, and 6 to N(alpha)-acetyl-lysine was explored at neutral pH. Adduct 2 did not react with N(alpha)-acetyl-lysine, whereas 4-6 readily formed cross-links. The structures of the cross-links were elucidated, and their stabilities were investigated. The results define the acidity of oxopropenyl deoxynucleosides and highlight its importance to their reactivity toward nucleophiles

  N2-氧代丙烯基脱氧鸟苷 (2) 通过用碱基丙烯醛或丙二醛修饰 dG 残基在双链 DNA 中形成。根据其闭环对嘧啶嘌呤酮衍生物 1 的 pH 依赖性，估计 2 的 pKa 为 6.9。 2 的酸度可能是其错误编码特性及其与 DNA 或蛋白质中的亲核试剂反应性的重要决定因素。为了检验这一假设，合成了 dA (4)、dC (5) 和 N1-甲基-dG (6) 的类似 N-氧代丙烯基衍生物，并通过光学滴定确定了它们的 pKa。dA 和 dC 的 N-氧代丙烯基衍生物均显示出 10.5 的 pKa，而 N1-甲基 dG 的 N-氧代丙烯基衍生物的 pKa 为 8.2。在中性 pH 值下探索了 2、4、5 和 6 与 N(α)-乙酰-赖氨酸的交联。加合物 2 不与 N(α)-乙酰-赖氨酸反应，而4-6容易形成交联。阐明了交联的结构，并研究了它们的稳定性。结果定义了氧代丙烯基脱氧核苷的酸度，并强调了其
• SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
  申请人：Janssen BioPharma, Inc.

  公开号：EP3466959A1

  公开（公告）日：2019-04-10

  Disclosed herein are nucleosides, nucleotides and analogs thereof of fomula (III), pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are compouns of formula (III) for use in methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

  本文公开了式(III)的核苷、核苷酸及其类似物，包括一种或多种核苷、核苷酸及其类似物的药物组合物，以及合成方法。本文还公开了式(III)化合物，用于用核苷、核苷酸及其类似物改善和/或治疗疾病和/或病症，包括副粘病毒和/或正粘病毒感染的方法。
• MR1 LIGANDS AND PHARMACEUTICAL COMPOSITIONS FOR IMMUNOMODULATION
  申请人：Universität Basel

  公开号：EP3889602A1

  公开（公告）日：2021-10-06

  The invention relates to a method for modulating an interaction between an MR1 polypeptide and an MR1-specific T cell receptor molecule, whereby a MR1 polypeptide is contacted with a MR1 ligand compound that is a nucleobase adduct product reflecting a state of metabolic distress of a eukaryotic cell. The invention further relates to the use of compounds identified as MR1 ligands in vaccination or modulation of an MR1-restricted immune response.

  本发明涉及一种调节MR1多肽与MR1特异性T细胞受体分子之间相互作用的方法，其中MR1多肽与MR1配体化合物接触，MR1配体化合物是反映真核细胞代谢窘迫状态的核碱基加合物产物。 本发明进一步涉及鉴定为 MR1 配体的化合物在疫苗接种或调节 MR1 限制性免疫反应中的用途。