2-iodo-N⁶-(2''-phenylethyl)adenosine | 313477-86-0

• 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: 2-iodo-N⁶-(2''-phenylethyl)adenosine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-[2-iodo-6-(2-phenylethylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 313477-86-0
• 化学式: C₁₈H₂₀IN₅O₄
• 分子量: 497.292
• InChiKey: ASDNHKWZVMLKOP-LSCFUAHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-苯乙胺 、 2-iodo-N⁶-(2''-phenylethyl)adenosine 在 N,N-二异丙基乙胺 作用下， 以 乙二醇甲醚 为溶剂， 反应 24.0h， 生成 N⁶-(2-phenylethyl)-2-<(phenylethyl)amino>adenosine
  参考文献：
  名称：

  Adenosine Analogues as Inhibitors of Trypanosoma brucei Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N⁶-Substituted Adenosine

  摘要：

  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.

  DOI：

  10.1021/jm000287a
• 作为产物：
  描述：

  [(2R,3R,4R,5R)-3,4-diacetyloxy-5-[2-iodo-6-(2-phenylethylamino)purin-9-yl]oxolan-2-yl]methyl acetate 在 氨 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 2-iodo-N⁶-(2''-phenylethyl)adenosine
  参考文献：
  名称：

  具有核苷结构的A3腺苷受体拮抗剂及其抗癌活性

  摘要：

  A3 腺苷受体 (AR) 在多种癌细胞类型中的过表达使其成为肿瘤诊断和治疗的有吸引力的靶标。因此，在寻找新的 A3AR 配体时，合成了一系列新的 2,N6-二取代腺苷 (Ados)，并在 AR 的放射性配体结合和功能测定中进行了测试。发现在 N6 位带有 2-苯乙氨基的衍生物比相应的 N6-(2,2-二苯乙基) 类似物具有更高的 A3AR 亲和力和选择性。在 cAMP 积累试验中，发现 2-Chloro-N6-phenylethylAdo (15) 是一种有效的全 A3AR 激动剂，Ki 为 0.024 nM，EC50 为 14 nM。与 15 不同，其他配体表现为 A3AR 拮抗剂，其浓度依赖性地降低细胞生长并对前列腺癌细胞系 PC3 发挥细胞抑制活性，显示出与参考完全激动剂 Cl-IB-MECA 引发的效果相当甚至更显着的效果。特别是 N6-(2,2-diphenylethyl)-2-phenylethynylAdo

  DOI：

  10.3390/ph15020164