(2R,3R,4S,5R)-2-[2-amino-6-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 120524-28-9

• 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-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: N⁶-cyclopentyl-2-aminoadenosine；(4S,2R,3R,5R)-2-[2-amino-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol；(2R,3R,4S,5R)-2-[2-amino-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 120524-28-9
• 化学式: C₁₅H₂₂N₆O₄
• 分子量: 350.377
• InChiKey: PYLVODBGSCAFQR-IDTAVKCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R,3R,4S,5R)-2-[2-amino-6-(cyclopentylamino)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 、 原甲酸三甲酯 在 sodium azide 作用下， 反应 24.0h， 生成 (4S,2R,3R,5R)-2-[6-(cyclopentylamino)-2-(1,2,3,4-tetraazolyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
  参考文献：
  名称：

  WO2006/125190

  摘要：

  公开号：
• 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 乙醇 、 乙腈 为溶剂， 反应 18.08h， 生成 (2R,3R,4S,5R)-2-[2-amino-6-(cyclopentylamino)-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

• C2,N6-Disubstituted adenosines: synthesis and structure-activity relationships
  作者：Bharat K. Trivedi、Robert F. Bruns

  DOI：10.1021/jm00128a002

  日期：1989.8

  Extracellular adenosine receptors have been divided into two major subtypes, called A1 and A2. Substitution of the adenosine molecule with appropriate groups at C2 or N6 is known to impart selectivity for the A2 receptor over the A1 receptor. In the present study, we investigated whether substitution at both C2 and N6 would have additive effects on the A2/A1 affinity ratio, thereby providing compounds

  细胞外腺苷受体已被分为两种主要的亚型，称为A1和A2。已知在C2或N6处具有适当基团的腺苷分子的取代赋予A2受体相对于A1受体的选择性。在本研究中，我们研究了在C2和N6处取代是否会对A2 / A1亲和力比产生累加效应，从而为化合物提供比目前可用的试剂更高的A2选择性。令人失望的是，仅当在N6处有一个A1选择性基团时，可加性似乎才成立。例如，A1-选择性激动剂N6-环戊基腺苷的2-（苯氨基）取代导致对A2受体的选择性变化了70倍，但对A2-选择性激动剂N6- [2- （3，
• A1 adenosine receptor agonists
  申请人：Elzein Elfatih

  公开号：US20060276428A1

  公开（公告）日：2006-12-07

  Disclosed are novel compounds that are partial and full A 1 adenosine receptor agonists having the structure of Formula I: which are useful for treating various disease states, in particular tachycardia and atrial flutter, angina, and myocardial infarction.

  本发明揭示了具有以下结构式I的部分和完全A1腺苷受体激动剂的新化合物，其可用于治疗各种疾病状态，特别是心动过速和心房颤动、心绞痛和心肌梗死。
• 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.
• TRIVEDI, BHARAT K.;BRUNS, ROBERT F., J. MED. CHEM., 32,(1989) N, C. 1667-1673
  作者：TRIVEDI, BHARAT K.、BRUNS, ROBERT F.

  DOI：——

  日期：——
• A1 ADENOSINE RECEPTOR AGONISTS
  申请人：CV THERAPEUTICS, INC.

  公开号：EP1883646A1

  公开（公告）日：2008-02-06