(1S,2R,3S,4R,5S)-4-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-(phenylethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide | 1619240-19-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1S,2R,3S,4R,5S)-4-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-(phenylethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
• 英文别名: (1S,2R,3S,4R,5S)-4-(6-((2-(3,4-difluorophenyl)cyclopropyl)amino)-2-(phenylethynyl)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0]hexane-1-carboxamide；(1S,2R,3S,4R,5S)-4-[6-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-2-(2-phenylethynyl)purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
• CAS: 1619240-19-5
• 化学式: C₃₀H₂₆F₂N₆O₃
• 分子量: 556.572
• InChiKey: KBYRELOSSRTWHH-PXBXEHGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (3aR,3bS,4aS,5R,5aS)-5-(6-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-2-iodo-9H-purin-9-yl)-N,2,2-trimethyltetrahydrocyclopropa[3,4]cyclopenta[1,2-d][1,3]dioxole-3b(3aH)-carboxamide 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三氟甲磺酸 、 三乙胺 作用下， 以 甲醇 、 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-(phenylethynyl)-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

文献信息

• Extended N6 substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor
  作者：Dilip K. Tosh、Silvia Paoletta、Zhoumou Chen、Steven M. Moss、Zhan-Guo Gao、Daniela Salvemini、Kenneth A. Jacobson

  DOI：10.1016/j.bmcl.2014.06.006

  日期：2014.8

  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.