(2R,3R,4S,5R)-2-[2-amino-6-(methylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 5059-59-6

• 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: (2R,3R,4S,5R)-2-[2-amino-6-(methylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: (2R,3S,4S,5R)-2-(2-amino-6-methylamino-purin-9-yl)-5-hydroxy-methyl-tetrahydrofuran-3,4-diol；2-amino-N⁶-methyl-adenosine；2-amino-N⁶-methyladenosine；N⁶-methyl-adenosine；2-amino-N⁶-methyl-adenosine；2-amino-6-methylamino-9-(β-D-ribofuranosyl)purine；(2R,3R,4S,5R)-2-(2-Amino-6-methylamino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol；(2R,3R,4S,5R)-2-[2-amino-6-(methylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 5059-59-6
• 化学式: C₁₁H₁₆N₆O₄
• 分子量: 296.286
• InChiKey: XTJPMALIPQWXDY-KQYNXXCUSA-N

物化性质

• 沸点：
  760.7±70.0 °C(Predicted)
• 密度：
  2.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2',3',5'-三乙酰鸟苷 在 二乙胺 、 三乙胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 16.08h， 生成 (2R,3R,4S,5R)-2-[2-amino-6-(methylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  鸟苷激活的特定G蛋白偶联受体的存在的证据

  摘要：

  从神经元和神经胶质细胞向细胞外释放的鸟苷在中枢神经系统中起着重要作用，包括神经保护作用。创新的DELFIA Eu-GTP结合测定法通过使用一系列新颖和已知的鸟苷衍生物来优化在大鼠脑膜上假定的鸟苷受体结合位点的表征。这些核苷分别通过修饰鸟苷的6和5'位置的嘌呤和糖部分来制备。这些实验的结果证明，鸟苷，6-硫代鸟苷及其衍生物激活了一个G蛋白偶联受体，该受体不同于特征明确的腺苷受体。

  DOI：

  10.1002/cmdc.201100100

文献信息

• Transformations of thiopyrimidine and thiopurine nucleosides following oxidation with dimethyldioxirane
  作者：Raffaele Saladino、Enrico Mincione、Claudia Crestini、Maurizio Mezzetti

  DOI：10.1016/0040-4020(96)00289-x

  日期：1996.5

  and convenient method for the synthesis of several pyrimidine and purine nucleosides by selective oxidation of thionucleosides with dimethyldioxirane is reported. Thioketo moieties in the C-4 position of the pyrimidine ring, and in the C-6, and C-8 positions of the purine ring are the domain of oxidative nucleophilic substitution. Thioketo moieties in the C-2 position of both purine and pyrimidine rings

  报道了通过用二甲基二环氧乙烷选择性氧化硫代核苷来合成几种嘧啶和嘌呤核苷的通用且方便的方法。嘧啶环的C-4位，嘌呤环的C-6和C-8位的Thioketo部分是氧化亲核取代的结构域。嘌呤和嘧啶环的C-2位的Thioketo部分是脱硫或二硫化物形成的区域。
• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Convenient Synthesis of 8-Amino-2′-deoxyadenosine
  作者：Miriam Frieden、Anna Aviñó、Ramon Eritja

  DOI：10.1081/ncn-120019521

  日期：2003.5

  We studied the behaviour of 8-azido-2'-deoxyadenosine and 8-bromo-2'-deoxyadenosine in aqueous solutions of ammonia and primary and secondary amines. Unexpectedly, 8-Azido-2'-deoxyadenosine is converted to 8-amino-2'-deoxyadenosine in excellent yields. The use of this reaction for the preparation of 8-aminoadenine derivatives needed for the preparation of oligonucleotides carrying 8-aminoadenine is

  我们研究了8-叠氮基2'-脱氧腺苷和8-溴-2'-脱氧腺苷在氨水和伯胺和仲胺水溶液中的行为。出乎意料的是，以优异的产率将8-叠氮基2'-脱氧腺苷转化为8-氨基-2'-脱氧腺苷。讨论了该反应在制备8-氨基腺嘌呤衍生物中的用途，所述8-氨基腺嘌呤衍生物是制备携带8-氨基腺嘌呤的寡核苷酸所需的。
• Inhibition of viruses
  申请人：Loakes David

  公开号：US20050043268A1

  公开（公告）日：2005-02-24

  Disclosed is a pharmaceutical composition comprising a ribonucleoside analogue in accordance with general formula (I) or (II) as herein defined in admixture with a physiologically acceptable excipient diluent or carrier.

  本发明公开了一种药物组合物，该组合物包含符合本文定义的通式（I）或（II）的核糖核苷类似物，并与生理学上可接受的赋形剂稀释剂或载体混合。
• Adenosine Analogues as Inhibitors of <i>Trypanosoma </i><i>b</i><i>rucei </i>Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N⁶-Substituted Adenosine
  作者：Jerome C. Bressi、Jungwoo Choe、Melinda T. Hough、Frederick S. Buckner、Wesley C. Van Voorhis、Christophe L. M. J. Verlinde、Wim G. J. Hol、Michael H. Gelb

  DOI：10.1021/jm000287a

  日期：2000.11.1

  As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N-6-, 2-amino-N-6-, and N-2-substituted adenosine analogues were synthesized and tested to establish structure-activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for NG-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N-6-[2 "-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 muM. 2-[[2 "-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 muM. To explore the potential of an additive effect that having the N-6 and N-2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N-6,N-2-disubstituted adenosine analogues to yield N-6-(2 " -phenylethyl)-2-[(2 " -phenylethyl)amino]adenosine (69) as a 30 muM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 Angstrom X-ray structure of a T, brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this "flipped and rotated" binding mode.