N⁶-methyl-2-(4-phenyl-1,2,3-triazol-1-yl)-9-(β-D-ribofuranosyl)adenine | 906670-49-3

• 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: N⁶-methyl-2-(4-phenyl-1,2,3-triazol-1-yl)-9-(β-D-ribofuranosyl)adenine
• 英文别名: 9-(β-D-ribofuranosyl)-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-6-methylamino-9H-purine；N-Methyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)adenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(methylamino)-2-(4-phenyltriazol-1-yl)purin-9-yl]oxolane-3,4-diol
• CAS: 906670-49-3
• 化学式: C₁₉H₂₀N₈O₄
• 分子量: 424.419
• InChiKey: OWSGIKNSPZUJAA-SCFUHWHPSA-N

物化性质

• 沸点：
  860.2±75.0 °C(Predicted)
• 密度：
  1.74±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2',3',5'-三-O-乙酰-6-氯-2-碘嘌呤核苷 在 copper(II) sulfate 、 sodium ascorbate sodium azide 、 sodium carbonate 、 copper(II) sulfate 、 sodium ascorbate 、 L-脯氨酸 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 58.0h， 生成 N⁶-methyl-2-(4-phenyl-1,2,3-triazol-1-yl)-9-(β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  2-Triazole-Substituted Adenosines:  A New Class of Selective A₃ Adenosine Receptor Agonists, Partial Agonists, and Antagonists

  摘要：

  “点击化学”被用来合成两类2-(1,2,3-三氮唑基)腺苷衍生物(1-14)。测定其在人A1、A2A和A3腺苷受体上的结合亲和力及其在A3腺苷受体上的相对效能。一些三氮唑-1-基衍生物显示出低纳摩尔级的A3受体亲和力、高水平的A3/A2A选择性比值以及中等到高的A3/A1比值。1,2,3-三氮唑-4-基衍生物的A3受体亲和力通常较低。在腺嘌呤C2位的位阻较大基团往往降低相对A3受体效能。因此，几个5'-OH衍生物似乎成为选择性A3受体拮抗剂，即化合物10，与A1受体相比具有260倍的结合选择性，并在A3受体模型中显示出特征的结合模式。相应的5'-乙基脲酰胺衍生物通常显示出较高的A3受体亲和力，并表现为空气满拮抗剂，即化合物17，具有910倍的A3/A1选择性。因此，N6-取代的2-(1,2,3-三氮唑基)-腺苷衍生物构成了一类基于核苷的高效且高选择性的A3受体拮抗剂、部分激动剂和激动剂的新颖化合物。

  DOI：

  10.1021/jm0608208

文献信息

• 1,2,3-Triazoles as leaving groups in purine chemistry: a three-step synthesis of N6-substituted-2-triazolyl-adenine nucleosides and photophysical properties thereof
  作者：Armands Kovaļovs、Irina Novosjolova、Ērika Bizdēna、Inga Bižāne、Lina Skardziute、Karolis Kazlauskas、Saulius Jursenas、Māris Turks

  DOI：10.1016/j.tetlet.2012.11.095

  日期：2013.2

  A novel three-step approach for the synthesis of N6-substituted-2-(1,2,3-triazol-1-yl)-adenine nucleosides is described. 2,6-Bis-(1,2,3-triazol-1-yl)purine nucleosides are obtained, which undergo regioselective nucleophilic aromatic substitution with amines at C(6). Thus, 1,2,3-triazoles are shown to be good leaving groups in purine chemistry. The title compounds exhibit interesting levels of fluorescence

  描述了用于合成N 6-取代的-2-（1,2,3-三唑-1-基）-腺嘌呤核苷的新颖的三步法。获得了2,6-双-（1,2,3-三唑-1-基）嘌呤核苷，这些核苷在C（6）处被胺进行了区域选择性亲核芳香取代。因此，在嘌呤化学中显示1,2,3-三唑是良好的离去基团。标题化合物显示出令人感兴趣的荧光水平，量子产率高达53％。
• Application of 2,6-diazidopurine derivatives in the synthesis of thiopurine nucleosides
  作者：Irina Novosjolova、Ērika Bizdēna、Māris Turks

  DOI：10.1016/j.tetlet.2013.09.095

  日期：2013.11

  2,6-Diazidopurine derivatives undergo double azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reactions to give 2,6-bis-(triazolyl)purine analogs, which undergo selective nucleophilic aromatic substitution with various thiols at C(6). This synthetic sequence produces nucleoside analogs with 6-alkyl/arylthio-2-(4-allcyl/aryl-1H-1,2,3-triazol-1-yl)purine bases. In contrast, glycosylated 2,6-diazidopurines exhibit reasonable C(2) selectivity in nucleophilic aromatic substitution with thiols. This permits the synthesis of 2-alkylthio-6-azido-purine derivatives, which after CuAAC provide the corresponding 2-alkylthio-6-triazolyl-purine analogs. The latter are also susceptible to nucleophilic aromatic substitution with amines at C(6). The above mentioned compounds are useful molecular platforms in terms of medicinal chemistry. (C) 2013 Elsevier Ltd. All rights reserved.
• 2-Triazole-Substituted Adenosines:  A New Class of Selective A₃ Adenosine Receptor Agonists, Partial Agonists, and Antagonists
  作者：Liesbet Cosyn、Krishnan K. Palaniappan、Soo-Kyung Kim、Heng T. Duong、Zhan-Guo Gao、Kenneth A. Jacobson、Serge Van Calenbergh

  DOI：10.1021/jm0608208

  日期：2006.12.1

  ''Click chemistry" was explored to synthesize two series of 2-(1,2,3-triazolyl) adenosine derivatives (1-14). Binding affinity at the human A(1), A(2A), and A(3)ARs (adenosine receptors) and relative efficacy at the A(3)AR were determined. Some triazol-1-yl analogues showed A(3)AR affinity in the low nanomolar range, a high ratio of A(3)/A(2A) selectivity, and a moderate-to-high A(3)/A(1) ratio. The 1,2,3-triazol-4-yl regiomers typically showed decreased A(3)AR affinity. Sterically demanding groups at the adenine C2 position tended to reduce relative A(3)AR efficacy. Thus, several 5'-OH derivatives appeared to be selective A(3)AR antagonists, i.e., 10, with 260-fold binding selectivity in comparison to the A(1)AR and displaying a characteristic docking mode in an A(3)AR model. The corresponding 5'-ethyluronamide analogues generally showed increased A(3)AR affinity and behaved as full antagonists, i.e., 17, with 910-fold A(3)/A(1) selectivity. Thus, N-6-substituted 2-( 1,2,3-triazolyl)-adenosine analogues constitute a novel class of highly potent and selective nucleoside-based A(3)AR antagonists, partial agonists, and agonists.

  “点击化学”被用来合成两类2-(1,2,3-三氮唑基)腺苷衍生物(1-14)。测定其在人A1、A2A和A3腺苷受体上的结合亲和力及其在A3腺苷受体上的相对效能。一些三氮唑-1-基衍生物显示出低纳摩尔级的A3受体亲和力、高水平的A3/A2A选择性比值以及中等到高的A3/A1比值。1,2,3-三氮唑-4-基衍生物的A3受体亲和力通常较低。在腺嘌呤C2位的位阻较大基团往往降低相对A3受体效能。因此，几个5'-OH衍生物似乎成为选择性A3受体拮抗剂，即化合物10，与A1受体相比具有260倍的结合选择性，并在A3受体模型中显示出特征的结合模式。相应的5'-乙基脲酰胺衍生物通常显示出较高的A3受体亲和力，并表现为空气满拮抗剂，即化合物17，具有910倍的A3/A1选择性。因此，N6-取代的2-(1,2,3-三氮唑基)-腺苷衍生物构成了一类基于核苷的高效且高选择性的A3受体拮抗剂、部分激动剂和激动剂的新颖化合物。