(2R,3R,4S,5R)-2-(6-((5-aminopentyl)amino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 64630-73-5

• 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-(6-((5-aminopentyl)amino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4S,5R)-2-[6-(5-aminopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 64630-73-5
• 化学式: C₁₅H₂₄N₆O₄
• 分子量: 352.393
• InChiKey: HNNMAJORJVJRSK-SDBHATRESA-N

物化性质

• 沸点：
  698.6±65.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.02
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  151.57
• 氢给体数：
  5.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2-(6-((5-aminopentyl)amino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 、 霉酚酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  霉酚酸的新缀合物及其抗增殖活性。

  摘要：

  在EDCI作为偶联剂的存在下，N 6-（ω-氨基烷基）腺苷与MPA的反应获得了新的霉酚酸（MPA）共轭物。在健康捐献者的白血病细胞系（Jurkat）和PBMC上评估了新化合物4a–h。接头的长度影响观察到的活性。具有1，3-二胺间隔基的化合物4b显示出最有希望的结果，可以考虑用于进一步的研究。

  DOI：

  10.1080/10286020.2016.1184653
• 作为产物：
  描述：

  1,5-二氨基戊烷 、 6-氯嘌呤核苷 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 (2R,3R,4S,5R)-2-(6-((5-aminopentyl)amino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  霉酚酸的新缀合物及其抗增殖活性。

  摘要：

  在EDCI作为偶联剂的存在下，N 6-（ω-氨基烷基）腺苷与MPA的反应获得了新的霉酚酸（MPA）共轭物。在健康捐献者的白血病细胞系（Jurkat）和PBMC上评估了新化合物4a–h。接头的长度影响观察到的活性。具有1，3-二胺间隔基的化合物4b显示出最有希望的结果，可以考虑用于进一步的研究。

  DOI：

  10.1080/10286020.2016.1184653

文献信息

• A Structure–Activity Relationship Study of Bitopic <i>N</i>⁶-Substituted Adenosine Derivatives as Biased Adenosine A₁ Receptor Agonists
  作者：Luigi Aurelio、Jo-Anne Baltos、Leigh Ford、Anh T. N. Nguyen、Manuela Jörg、Shane M. Devine、Celine Valant、Paul J. White、Arthur Christopoulos、Lauren T. May、Peter J. Scammells

  DOI：10.1021/acs.jmedchem.8b00047

  日期：2018.3.8

  prototypical A1AR agonists has been hindered due to dose limiting adverse effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting of an adenosine pharmacophore linked to an allosteric moiety, could stimulate cardioprotective A1AR signaling in the absence of unwanted bradycardia. Therefore, this study aimed to investigate the structure–activity relationship of compound 1 biased

  腺苷A 1受体（A 1 AR）是心肌缺血再灌注损伤的潜在新型治疗靶标。但是，迄今为止，由于剂量限制的不良反应，原型A 1 AR激动剂的临床翻译受到了阻碍。最近，我们证明，由连接至变构部分的腺苷药效基团组成的偏向性双位激动剂1可以在不存在心动过缓的情况下刺激心脏保护性A 1 AR信号传导。因此，本研究旨在研究化合物1激动剂的构效关系。一系列的新的衍生物的1合成并进行药理学分析。对正构腺苷药效团，接头和变构2-氨基-3-苯甲酰基噻吩药效团进行了修饰，以探究其结构-活性关系，特别是在信号偏向方面以及A 1 AR活性和亚型选择性方面。总的来说，我们的发现表明，变构部分，特别是噻吩支架的4-（三氟甲基）苯基取代基，在赋予A 1 AR上的双位配体偏倚方面很重要。
• 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.
• Examining the Role of the Linker in Bitopic <i>N</i>⁶-Substituted Adenosine Derivatives Acting as Biased Adenosine A₁ Receptor Agonists
  作者：Jon Kyle Awalt、Anh T.N. Nguyen、Tim J. Fyfe、Bui San Thai、Paul J. White、Arthur Christopoulos、Manuela Jörg、Lauren T. May、Peter J. Scammells

  DOI：10.1021/acs.jmedchem.2c00320

  日期：2022.7.14