ethyl (3aR,3bS,4aS,5R,5aS)-5-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate | 1619240-28-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: ethyl (3aR,3bS,4aS,5R,5aS)-5-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate
• CAS: 1619240-28-6
• 化学式: C₂₆H₂₆F₂IN₅O₄
• 分子量: 637.425
• InChiKey: FWTILAAQYXGCQI-CVRAKIJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  100.39
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  ethyl (3aR,3bS,4aS,5R,5aS)-5-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (1S,2R,3S,4R,5S)-4-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-(pyridin-2-ylethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
  参考文献：
  名称：

  Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor

  摘要：

  2-Arylethynyl-(N)-methanocarba adenosine 5'-methyluronamides containing rigid N-6-(trans-2-phenylcyclopropyl) and 2-phenylethynyl groups were synthesized as agonists for probing structural features of the A(3) adenosine receptor (AR). Radioligand binding confirmed A(3)AR selectivity and N-6-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N-6 groups was explored by docking to an A(3)AR homology model, indicating specific hydrophobic interactions with the second extracellular loop able to modulate the affinity profile. 2-Pyridylethynyl derivative 18 was administered orally in mice to reduce chronic neuropathic pain in the chronic constriction injury model. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.06.006
• 作为产物：
  描述：

  (1'S,2'R,3'S,4'R,5'S)-4'-[6-chloro-2-iodopurin-9-yl]-2',3'-isopropylidenebicyclo[3.1.0]hexane-1'-carboxylic acid ethyl ester 、 (1R,2S)-2-(3,4-二氟苯基)环丙胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 以69%的产率得到ethyl (3aR,3bS,4aS,5R,5aS)-5-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxylate
  参考文献：
  名称：

  Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor

  摘要：

  2-Arylethynyl-(N)-methanocarba adenosine 5'-methyluronamides containing rigid N-6-(trans-2-phenylcyclopropyl) and 2-phenylethynyl groups were synthesized as agonists for probing structural features of the A(3) adenosine receptor (AR). Radioligand binding confirmed A(3)AR selectivity and N-6-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N-6 groups was explored by docking to an A(3)AR homology model, indicating specific hydrophobic interactions with the second extracellular loop able to modulate the affinity profile. 2-Pyridylethynyl derivative 18 was administered orally in mice to reduce chronic neuropathic pain in the chronic constriction injury model. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.06.006