(2R,3S,4S,5R)-2-(2-cyano-6-methylamino-purin-9-yl)-5-hydroxy-methyl-tetrahydrofuran-3,4-diol | 750644-43-0

• 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: (2R,3S,4S,5R)-2-(2-cyano-6-methylamino-purin-9-yl)-5-hydroxy-methyl-tetrahydrofuran-3,4-diol
• 英文别名: 2-cyano-N⁶-methyl adenosine；9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(methylamino)purine-2-carbonitrile
• CAS: 750644-43-0
• 化学式: C₁₂H₁₄N₆O₄
• 分子量: 306.281
• InChiKey: CFDILUOQELMYMS-JJNLEZRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  149
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  溶剂黄146 、 (2R,3S,4S,5R)-2-(2-cyano-6-methylamino-purin-9-yl)-5-hydroxy-methyl-tetrahydrofuran-3,4-diol 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以36%的产率得到(2R,3S,4S,5R)-2-(2-aminomethyl-6-methylamino-purin-9-yl)-5-hydroxymethyl-tetrahydrofuran-3,4-diol acetic acid salt
  参考文献：
  名称：

  Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position

  摘要：

  We studied the structural determinants of binding affinity and efficacy of adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine were combined with N-6-substitutions known to enhance human A(3)AR affinity. Selectivity of binding of the analogues and their functional effects on cAMP production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs. Mainly sterically small substituents at the 2-position modulated both the affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased hA(3)AR affinity and efficacy in the cases of N-6-(3-iodobenzyl) and N-6-(trans-2-phenyl-1-cyclopropyl), for which a full AAR agonist was converted into a selective antagonist; the 2-cyano-N-6-methyl analogue was a full A(3)AR agonist. The combination of N-6-benzyl and various 2-substitutions (chloro, trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.031
• 作为产物：
  描述：

  2-amino-6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 亚硝酸特丁酯 、 三(2-呋喃基)膦 、 二碘甲烷 、 1,1,3,3-四甲基脲 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 54.0h， 生成 (2R,3S,4S,5R)-2-(2-cyano-6-methylamino-purin-9-yl)-5-hydroxy-methyl-tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  Modulation of adenosine receptor affinity and intrinsic efficacy in adenine nucleosides substituted at the 2-position

  摘要：

  We studied the structural determinants of binding affinity and efficacy of adenosine receptor (AR) agonists. Substituents at the 2-position of adenosine were combined with N-6-substitutions known to enhance human A(3)AR affinity. Selectivity of binding of the analogues and their functional effects on cAMP production were studied using recombinant human A(1), A(2A), A(2B), and A(3)ARs. Mainly sterically small substituents at the 2-position modulated both the affinity and intrinsic efficacy at all subtypes. The 2-cyano group decreased hA(3)AR affinity and efficacy in the cases of N-6-(3-iodobenzyl) and N-6-(trans-2-phenyl-1-cyclopropyl), for which a full AAR agonist was converted into a selective antagonist; the 2-cyano-N-6-methyl analogue was a full A(3)AR agonist. The combination of N-6-benzyl and various 2-substitutions (chloro, trifluoromethyl, and cyano) resulted in reduced efficacy at the A(1)AR. The environment surrounding the 2-position within the putative A(3)AR binding site was explored using rhodopsin-based homology modeling and ligand docking. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.031