(-)-(2R,3R,4S)-2-(6-amino-2-(hex-1-ynyl)-9H-purin-9-yl)-tetrahydrothiophene-3,4-diol | 1246034-00-3

• 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: (-)-(2R,3R,4S)-2-(6-amino-2-(hex-1-ynyl)-9H-purin-9-yl)-tetrahydrothiophene-3,4-diol
• 英文别名: (2R,3R,4S)-2-(6-amino-2-(hex-1-ynyl)-9H-purin-9-yl)tetrahydrothiophene-3,4-diol；(2R,3R,4S)-2-(6-amino-2-hex-1-ynylpurin-9-yl)thiolane-3,4-diol
• CAS: 1246034-00-3
• 化学式: C₁₅H₁₉N₅O₂S
• 分子量: 333.414
• InChiKey: VQABXXYIDMPKKB-DDHOLCJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-碘-6-氯嘌呤 在 盐酸 、 copper(l) iodide 、 四(三苯基膦)钯 、 N,O-双三甲硅基乙酰胺 、 氨 、 caesium carbonate 、 叔丁醇 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 29.75h， 生成 (-)-(2R,3R,4S)-2-(6-amino-2-(hex-1-ynyl)-9H-purin-9-yl)-tetrahydrothiophene-3,4-diol
  参考文献：
  名称：

  Structure–Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A_2A and A₃ Adenosine Receptor Ligands

  摘要：

  Truncated N-6-substituted-4'-oxo- and 4'-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A(2A) and A(3) adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA(2A)AR, but hydrophobic C8 substitution abolished binding at the hA(2A)AR. However, most of synthesized compounds displayed medium to high binding affinity at the hA(3)AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA(2A)AR agonists. C2 substitution probed geometrically through hA(2A)ARdocking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA(2A)AR agonist and hA(3)AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.

  DOI：

  10.1021/jm201229j

文献信息

• Discovery of A New Human A_2A Adenosine Receptor Agonist, Truncated 2-Hexynyl-4′-thioadenosine
  作者：Xiyan Hou、Hea Ok Kim、Varughese Alexander、Kyunglim Kim、Sun Choi、Seul-gi Park、Jin Hee Lee、Lena S. Yoo、Zhan-Guo Gao、Kenneth A. Jacobson、Lak Shin Jeong

  DOI：10.1021/ml1001823

  日期：2010.12.9

  The truncated C2- and C8-substituted 4'-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-Catalyzed cross-coupling reactions as key steps. In this study, an A(3) adenosine receptor. (AR) antagonist, truncated 4'-thioadenosine derivative 3, was successfully converted into a potent A(2A) AR agonist 4a (K-i = 7.19 +/- 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N-6-substituted. However, C8-substitution greatly reduced binding affinity at the human A(2A) AR. All synthesized compounds 4a-d maintained their affinity at the human A(3) AR, but 4a was found to be a competitive A(3) AR antagonist/A(2A) AR agonist in cyclic AMP assays. This study indicates that the truncated C2-substituted 4'-thioadenosine derivatives 4a and 4b can serve as novel templates for the development of new A(2A) AR ligands.