4-methylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine | 13241-46-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-methylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-[4-(methylamino)pyrrolo[2,3-d]pyrimidin-7-yl]tetrahydrofuran-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[4-(methylamino)pyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol
• CAS: 13241-46-8
• 化学式: C₁₂H₁₆N₄O₄
• 分子量: 280.283
• InChiKey: VEMBQZKPZAZEFQ-MFYTUXHUSA-N

物化性质

• 熔点：
  173-176 °C(Solv: water (7732-18-5))
• 沸点：
  626.0±55.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-methylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 在 吡啶 、 4-二甲氨基吡啶 、 silver nitrate 、 三乙胺 作用下， 反应 38.5h， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O-(tert-butyldimethylsilyl)-N⁶-methyl-7-deazaadenosine
  参考文献：
  名称：

  N6-甲基腺苷的原子突变揭示了人类 m6A 阅读器和擦除器蛋白的独特识别模式

  摘要：

  N 6 -甲基腺苷 (m 6 A) 是细胞 RNA 中重要的修饰核苷，与多种细胞过程相关，并与疾病有关。与 m 6 A 动态安装和去除相关的酶是药物研究中重点研究的目标，这需要详细了解蛋白质对 m 6 A 的识别模式。在这里，我们利用 m 6 A 的原子诱变系统地研究了两种人类 m 6 A 去甲基化酶 FTO 和 ALKBH5 的机制以及 YTH 阅读器蛋白 YTHDF2/DC1/DC2 的结合模式。原子诱变是指通过化学合成引入的原子特异性变化，例如用碳原子取代氮。通过固相合成制备含有位点特异性掺入的1-脱氮-、3-脱氮-和7-脱氮-m 6 A核苷的合成RNA寡核苷酸，并评估它们的RNA结合和重组蛋白的去甲基化。我们发现底物识别和转化存在明显差异，并揭示了酶活性的结构偏好。这项工作中引入的 deaza m 6 A 类似物将成为 m 6 A 研究中其他蛋白质的有用探针。

  DOI：

  10.1021/jacs.4c00626
• 作为产物：
  描述：

  (2R,3R,4R,5R)-2-((苯甲酰氧基)甲基)-5-(4-氯-5-碘-7H-吡咯并[2 在 lithium chloro-isopropyl-magnesium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.5h， 生成 4-methylamino-N7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis, Cytostatic, Antimicrobial, and Anti-HCV Activity of 6-Substituted 7-(Het)aryl-7-deazapurine Ribonucleosides

  摘要：

  A series of 80 7-(het)aryl- and 7-ethyny1-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)ary1-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.

  DOI：

  10.1021/jm4018948

文献信息

• NOVEL SUBSTITUTED 7-DEAZAPURINE RIBONUCLEOSIDES FOR THERAPEUTIC USES
  申请人：Institute of Organic Chemistry and Biochemistry ASCR, v.v.i.

  公开号：US20160159844A1

  公开（公告）日：2016-06-09

  Compounds of Formula I and a pharmaceutically acceptable salt thereof, an optical isomer thereof, or a mixture of optical isomers thereof, as well as compositions which include such compounds and therapeutic methods that utilize such compounds and/or compositions.

  化合物I的盐，其药用上可以接受的盐，其光学异构体或其光学异构体的混合物，以及包括这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。
• Atomic Mutagenesis of <i>N</i>⁶-Methyladenosine Reveals Distinct Recognition Modes by Human m⁶A Reader and Eraser Proteins
  作者：Florian Seitz、Tina Jungnickel、Nicole Kleiber、Jens Kretschmer、Julia Dietzsch、Juliane Adelmann、Katherine E. Bohnsack、Markus T. Bohnsack、Claudia Höbartner

  DOI：10.1021/jacs.4c00626

  日期：2024.3.20

  atom-specific changes that are introduced by chemical synthesis, such as the replacement of nitrogen by carbon atoms. Synthetic RNA oligonucleotides containing site-specifically incorporated 1-deaza-, 3-deaza-, and 7-deaza-m6A nucleosides were prepared by solid-phase synthesis and their RNA binding and demethylation by recombinant proteins were evaluated. We found distinct differences in substrate recognition

  N 6 -甲基腺苷 (m 6 A) 是细胞 RNA 中重要的修饰核苷，与多种细胞过程相关，并与疾病有关。与 m 6 A 动态安装和去除相关的酶是药物研究中重点研究的目标，这需要详细了解蛋白质对 m 6 A 的识别模式。在这里，我们利用 m 6 A 的原子诱变系统地研究了两种人类 m 6 A 去甲基化酶 FTO 和 ALKBH5 的机制以及 YTH 阅读器蛋白 YTHDF2/DC1/DC2 的结合模式。原子诱变是指通过化学合成引入的原子特异性变化，例如用碳原子取代氮。通过固相合成制备含有位点特异性掺入的1-脱氮-、3-脱氮-和7-脱氮-m 6 A核苷的合成RNA寡核苷酸，并评估它们的RNA结合和重组蛋白的去甲基化。我们发现底物识别和转化存在明显差异，并揭示了酶活性的结构偏好。这项工作中引入的 deaza m 6 A 类似物将成为 m 6 A 研究中其他蛋白质的有用探针。
• N-modification of 7-Deazapurine nucleoside analogues as Anti-Trypanosoma cruzi and anti-Leishmania agents: Structure-activity relationship exploration and In vivo evaluation
  作者：Cai Lin、Denise da Gama Jaén Batista、Ana Lia Mazzeti、Roberson Donola Girão、Gabriel Melo de Oliveira、Izet Karalic、Fabian Hulpia、Maria de Nazaré C. Soeiro、Louis Maes、Guy Caljon、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2022.114165

  日期：2022.3
• US9586986B2
  申请人：——

  公开号：US9586986B2

  公开（公告）日：2017-03-07
• Synthesis, Cytostatic, Antimicrobial, and Anti-HCV Activity of 6-Substituted 7-(Het)aryl-7-deazapurine Ribonucleosides
  作者：Petr Nauš、Olga Caletková、Petr Konečný、Petr Džubák、Kateřina Bogdanová、Milan Kolář、Jana Vrbková、Lenka Slavětínská、Eva Tloušt’ová、Pavla Perlíková、Marián Hajdúch、Michal Hocek

  DOI：10.1021/jm4018948

  日期：2014.2.13

  A series of 80 7-(het)aryl- and 7-ethyny1-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was studied and compared with that of the parent 7-(het)ary1-7-deazaadenosine series. Several of the compounds, in particular 6-substituted 7-deazapurine derivatives bearing a furyl or ethynyl group at position 7, were significantly cytotoxic at low nanomolar concentrations whereas most were much less potent or inactive. Promising activity was observed with some compounds against Mycobacterium bovis and also against hepatitis C virus in a replicon assay.