(1'R,2'S,3'R,4'R)-1-[2,3-dihydroxy-4-(hydroxymethyl)cyclopentan-1-yl]-6-(4-methyl-sulfonylbenzylthio)purine | 1233860-61-1

• 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: (1'R,2'S,3'R,4'R)-1-[2,3-dihydroxy-4-(hydroxymethyl)cyclopentan-1-yl]-6-(4-methyl-sulfonylbenzylthio)purine
• 英文别名: (1S,2R,3R,5R)-3-(hydroxymethyl)-5-[6-[(4-methylsulfonylphenyl)methylsulfanyl]purin-9-yl]cyclopentane-1,2-diol
• CAS: 1233860-61-1
• 化学式: C₁₉H₂₂N₄O₅S₂
• 分子量: 450.539
• InChiKey: GDHTVTHUCPOZER-WNOSKKOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  172
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (1'R,2'S,3'R,4'R)-9-[2,3-dihydroxy-4-(hydroxymethyl)-cyclopentan-1-yl]-6-mercaptopurine 、 4-(methylsulfonyl)benzyl bromide 在 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 11.0h， 以88%的产率得到(1'R,2'S,3'R,4'R)-1-[2,3-dihydroxy-4-(hydroxymethyl)cyclopentan-1-yl]-6-(4-methyl-sulfonylbenzylthio)purine
  参考文献：
  名称：

  Structure–activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase

  摘要：

  Carbocyclic 6-benzylthioinosine analogues were synthesized and evaluated for their binding affinity against Toxoplasma gondii adenosine kinase [EC.2.7.1.20]. Various substituents on the aromatic ring of the 6-benzylthio group resulted in increased binding affinity to the enzyme as compared to the unsubstituted compound. Carbocyclic 6-(p-methylbenzylthio)inosine 9n exhibited the most potent binding affinity. Docking simulations were performed to position compound 9n into the T. gondii adenosine kinase active site to determine the probable binding mode. Experimental investigations and theoretical calculations further support that an oxygen atom of the sugar is not critical for the ligand-binding. In agreement with its binding affinity, carbocyclic 6-(p-methylbenzylthio) inosine 9n demonstrated significant anti-toxoplasma activity (IC(50) = 11.9 mu M) in cell culture without any apparent host-toxicity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.003

文献信息

• Structure–activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase
  作者：Young Ah Kim、Ravindra K. Rawal、Jakyung Yoo、Ashoke Sharon、Ashok K. Jha、Chung K. Chu、Reem H. Rais、Omar N. Al Safarjalani、Fardos N.M. Naguib、Mahmoud H. el Kouni

  DOI：10.1016/j.bmc.2010.04.003

  日期：2010.5

  Carbocyclic 6-benzylthioinosine analogues were synthesized and evaluated for their binding affinity against Toxoplasma gondii adenosine kinase [EC.2.7.1.20]. Various substituents on the aromatic ring of the 6-benzylthio group resulted in increased binding affinity to the enzyme as compared to the unsubstituted compound. Carbocyclic 6-(p-methylbenzylthio)inosine 9n exhibited the most potent binding affinity. Docking simulations were performed to position compound 9n into the T. gondii adenosine kinase active site to determine the probable binding mode. Experimental investigations and theoretical calculations further support that an oxygen atom of the sugar is not critical for the ligand-binding. In agreement with its binding affinity, carbocyclic 6-(p-methylbenzylthio) inosine 9n demonstrated significant anti-toxoplasma activity (IC(50) = 11.9 mu M) in cell culture without any apparent host-toxicity. (C) 2010 Elsevier Ltd. All rights reserved.