(S)-4-(6-amino-9-methyl-9H-purin-2-yl)but-3-yn-2-ol | 1443762-92-2

• 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: (S)-4-(6-amino-9-methyl-9H-purin-2-yl)but-3-yn-2-ol
• 英文别名: (2S)-4-(6-amino-9-methylpurin-2-yl)but-3-yn-2-ol
• CAS: 1443762-92-2
• 化学式: C₁₀H₁₁N₅O
• 分子量: 217.23
• InChiKey: JVPHTWLHPCXPHA-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  89.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-4-(6-amino-9-methyl-9H-purin-2-yl)but-3-yn-2-ol 在 10% Pd/C 、 氢气 、 溴 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， -14.0~90.0 ℃ 、405.33 kPa 条件下， 反应 56.33h， 生成 ST5748
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535), A Potent Antagonist of the A_2A Adenosine Receptor for the Treatment of Parkinson’s Disease

  摘要：

  The synthesis and preliminary in vitro evaluation of five metabolites of the A(2A) antagonist ST1535 (1) are reported. The metabolites, originating in vivo from enzymatic oxidation of 2-butyl group of parent compound, were synthesized from 6-chloro-2-iodo-9-methyl-9H-purine (2) by selective C-C bond formation via halogen/magnesium exchange and/or palladium-catalyzed reactions. The metabolites behaved in vitro as antagonist, ligands of cloned human A(2A), receptor with affinities (K-i 7.5-53 nM) comparable to that of compound 1 (K-i 10.7 nM), thus showing that the long duration of action of 1 could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.

  DOI：

  10.1021/jm400491x
• 作为产物：
  描述：

  6-chloro-2-iodo-9-methyl-9H-purine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氨 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 17.5h， 生成 (S)-4-(6-amino-9-methyl-9H-purin-2-yl)but-3-yn-2-ol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Metabolites of 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine (ST1535), A Potent Antagonist of the A_2A Adenosine Receptor for the Treatment of Parkinson’s Disease

  摘要：

  The synthesis and preliminary in vitro evaluation of five metabolites of the A(2A) antagonist ST1535 (1) are reported. The metabolites, originating in vivo from enzymatic oxidation of 2-butyl group of parent compound, were synthesized from 6-chloro-2-iodo-9-methyl-9H-purine (2) by selective C-C bond formation via halogen/magnesium exchange and/or palladium-catalyzed reactions. The metabolites behaved in vitro as antagonist, ligands of cloned human A(2A), receptor with affinities (K-i 7.5-53 nM) comparable to that of compound 1 (K-i 10.7 nM), thus showing that the long duration of action of 1 could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.

  DOI：

  10.1021/jm400491x

文献信息

• Synthesis and Biological Evaluation of Metabolites of 2-<i>n</i>-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9<i>H</i>-purin-6-ylamine (ST1535), A Potent Antagonist of the A_2A Adenosine Receptor for the Treatment of Parkinson’s Disease
  作者：Giovanni Piersanti、Francesca Bartoccini、Simone Lucarini、Walter Cabri、Maria Antonietta Stasi、Teresa Riccioni、Franco Borsini、Giorgio Tarzia、Patrizia Minetti

  DOI：10.1021/jm400491x

  日期：2013.7.11

  The synthesis and preliminary in vitro evaluation of five metabolites of the A(2A) antagonist ST1535 (1) are reported. The metabolites, originating in vivo from enzymatic oxidation of 2-butyl group of parent compound, were synthesized from 6-chloro-2-iodo-9-methyl-9H-purine (2) by selective C-C bond formation via halogen/magnesium exchange and/or palladium-catalyzed reactions. The metabolites behaved in vitro as antagonist, ligands of cloned human A(2A), receptor with affinities (K-i 7.5-53 nM) comparable to that of compound 1 (K-i 10.7 nM), thus showing that the long duration of action of 1 could be in part due to its metabolites. General behavior after oral administration in mice was also analyzed.