N6-(2,2-diphenylethyl)-2-aminoadenosine | 98383-43-8

• 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-(2,2-diphenylethyl)-2-aminoadenosine
• 英文别名: (2R,3R,4S,5R)-2-[2-amino-6-(2,2-diphenylethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 98383-43-8
• 化学式: C₂₄H₂₆N₆O₄
• 分子量: 462.508
• InChiKey: DWLRQCKPLTUZSI-ZDXOVATRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  6-氯鸟嘌呤核苷 、 2,2-二苯基乙胺 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 N6-(2,2-diphenylethyl)-2-aminoadenosine
  参考文献：
  名称：

  C2，N6-二取代的腺苷：合成与结构-活性关系。

  摘要：

  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，

  DOI：

  10.1021/jm00128a002

文献信息

• N.sup.6 -substituted adenosines for treating pain
  申请人：Warner-Lambert Company

  公开号：US04657897A1

  公开（公告）日：1987-04-14

  N.sup.6 -Substituted diarylalkyladenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.

  N.sup.6-取代的二芳基烷基腺苷及其具有极具吸引力的中枢神经系统和心血管特性的药用可接受的酸盐，描述了其制造过程和药用组合物以及使用所述化合物和组合物的方法。
• Method for treating schizophrenia and medicaments therefor
  申请人：Warner-Lambert Company

  公开号：US04582823A1

  公开（公告）日：1986-04-15

  A method for treating schizophrenia without precipitating neurological side effects such as extrapyramidal syndrome and tardive dyskinesia by administering prior to or concomitantly with haloperidol a diphenylalkyladenosine or diphenylalkyl-2-amino-adenosine is described as well as pharmaceutical compositions therefor.

  本文描述了一种治疗精神分裂症的方法，该方法在给予氟哌啶醇之前或同时给予二苯基烷基腺苷或二苯基烷基-2-氨基腺苷，以避免出现额外锥体外症候群和迟发性运动障碍，同时还提供了相应的制药组合物。
• N.sup.6 -substituted adenosines and method of use
  申请人：Warner-Lambert Company

  公开号：US04657898A1

  公开（公告）日：1987-04-14

  N.sup.6 -Substituted diarylalkyladenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions are described.

  本文描述了N.sup.6-取代二芳基烷基腺苷及其药学上可接受的酸盐，具有高度理想的中枢神经系统和心血管特性，以及制造这些化合物的过程和制药组合物，以及使用这些化合物和组合物的方法。
• N6- substituted diarylalkyl adenosines, processes for their production and pharmaceutical compositions comprising the same
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0251339A2

  公开（公告）日：1988-01-07

  N⁶-Substituted diarylalkyladenosines of the formula: are disclosed. Processes for their manufacture and pharmaceutical compositions containing the same are also disclosed. The compounds have highly desirable central-nervous system and cardio-vascular properties.

  本发明公开了式：的 N⁶-取代二芳基烷基腺苷，还公开了其生产工艺和含有这些化合物的药物组合物。 这些化合物具有非常理想的中枢神经系统和心血管特性。
• 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.