5'-N-(2-fluoroethyl)-2',3'-O-isopropylidene-carboxamidoadenosine

• 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: 5'-N-(2-fluoroethyl)-2',3'-O-isopropylidene-carboxamidoadenosine
• 英文别名: (3aR,4R,6S,6aS)-4-(6-aminopurin-9-yl)-N-(2-fluoroethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide
• 化学式: C₁₅H₁₉FN₆O₄
• 分子量: 366.352
• InChiKey: HHBOZEMJCUCRPF-QOBXEIRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-N-(2-fluoroethyl)-2',3'-O-isopropylidene-carboxamidoadenosine 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以23 mg的产率得到(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-N-(2-fluoroethyl)-3,4-dihydroxytetrahydrofuran-2-carboxamide
  参考文献：
  名称：

  Optimization of Adenosine 5′-Carboxamide Derivatives as Adenosine Receptor Agonists Using Structure-Based Ligand Design and Fragment Screening

  摘要：

  Structures of G protein-coupled receptors (GPCRs) have a proven utility in the discovery of new antagonists and inverse ago fists modulating signaling of this important family of clinical targets. Applicability of active-state GPCR structures to virtual screening and rational optimization of agonists, however, remains to be assessed. In this study of adenosine 5' derivatives, we evaluated the performance of an agonist-bound A(2A) adenosine receptor (AR) structure in retrieval of known agonists and then employed the structure to screen for new fragments optimally fitting the corresponding subpocket. Biochemical and functional assays demonstrate high affinity of new derivatives that include polar heterocycles. The binding models also explain modest selectivity gain for some substituents toward the closely related A(1)AR subtype and the modified agonist efficacy of some of these ligands. The study suggests further applicability of in silico fragment screening to rational lead optimization in GPCRs.

  DOI：

  10.1021/jm300095s
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 吡啶 、 氢氧化钾 、 potassium permanganate 、 N,N'-二异丙基碳二亚胺 作用下， 以 水 为溶剂， 反应 74.0h， 生成 5'-N-(2-fluoroethyl)-2',3'-O-isopropylidene-carboxamidoadenosine
  参考文献：
  名称：

  Synthesis of 5?-N-(2-[18F]fluoroethyl)-carboxamidoadenosine: a promising tracer for investigation of adenosine receptor system by PET technique

  摘要：

  5'-N-(2-[F-18]Fluoroethyl)-carboxamidoadenosine ([F-18]FNECA), a promising F-18-labelled adenosine agonist has been prepared by two different synthetic routes. In the first, [F-18]fluoride was reacted with 5'-N,N-ethylene-2',3'-O-isopropylidenecarboxamido-adenosine and after removing the protective group [F-18]FNECA was obtained in a low radiochemical yield (1+/-1%, mean+/-sd, n=7, decay corrected). In the second, 2-[F-18]fluoroethylamine was synthesised according to the literature and reacted with 2',3'-O-isopropylideneadenosine-5'-uronic acid in the presence of a coupling agent. The following hydrolysis step provided the [F-18]FNECA with a modest radiochemical yield (24+/-9%, n=17, based on [F-18]fluoride-activity). After purification by preparative reverse phase HPLC 18.9-166.5 MBq (0.51-4.5 mCi) [F-18]FNECA was obtained with a specific activity of 2.35+/-1.14 TBq/mmol (63.5+/-30.9 Ci/mmol, n=3). The total synthesis took 200 min and the decay corrected radiochemical yield based on [F-18]F- activity was 17+/-9% (n=5) with more than 99.9% radiochemical purity. This second route provides sufficient [F-18]FNECA for the subsequent biological evaluation using PET-technique.

  DOI：

  10.1002/1099-1344(200007)43:8<807::aid-jlcr365>3.0.co;2-k