9-(2-Methoxy-benzyl)-6-(4-nitro-benzylsulfanyl)-9H-purine | 791077-86-6

• 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: 9-(2-Methoxy-benzyl)-6-(4-nitro-benzylsulfanyl)-9H-purine
• 英文别名: 9-[(2-methoxyphenyl)methyl]-6-[(4-nitrophenyl)methylsulfanyl]purine
• CAS: 791077-86-6
• 化学式: C₂₀H₁₇N₅O₃S
• 分子量: 407.453
• InChiKey: XEFUKNBCEIGCIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-(2-Methoxy-benzyl)-6-(4-nitro-benzylsulfanyl)-9H-purine 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到2-[6-(4-nitro-benzylsulfanyl)-purin-9-ylmethyl]-phenol
  参考文献：
  名称：

  Inhibition of Nucleoside Transport by New Analogues of 4-Nitrobenzylthioinosine:  Replacement of the Ribose Moiety by Substituted Benzyl Groups

  摘要：

  4-Nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside transport protein ENT1. However, its highly polar nature is unfavorable for oral absorption and/or penetration into the CNS. In the search for compounds with lower polarity than NBTI we replaced its ribose moiety by substituted benzyl groups. Halogen, hydroxyl, (trifluoro)methyl(-oxy), nitro, and amine functionalities were among the substituents at the benzyl group. In general, substitution of the benzyl group resulted in a lower affinity for ENT1. Only 2-hydroxyl substitution showed a higher affinity. Most likely this is the result of hydrogen bonding. Substitution at the 2-position of the benzyl group with aryl groups was also addressed. Compared to parent compound carrying a 2-phenylbenzyl group, all synthesized analogues gave higher affinities. Introduction of fluoro, trifluoromethyl, methoxy, and hydroxyl groups at the phenyl group clearly showed that addition to the 4-position was preferable. Despite the highly different character of a ribose and a benzyl group, K-i values in the low nanomolar range were obtained for the benzyl-substituted derivatives. Compound 35, LUF5919, and compound 60, LUF5929, displayed the highest affinity (K-i = 39 nM for both compounds), having a polar surface area of 101 Angstrom(2) and 85 Angstrom(2), respectively.

  DOI：

  10.1021/jm049735v
• 作为产物：
  描述：

  对硝基溴化苄 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.08h， 生成 9-(2-Methoxy-benzyl)-6-(4-nitro-benzylsulfanyl)-9H-purine
  参考文献：
  名称：

  Inhibition of Nucleoside Transport by New Analogues of 4-Nitrobenzylthioinosine:  Replacement of the Ribose Moiety by Substituted Benzyl Groups

  摘要：

  4-Nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside transport protein ENT1. However, its highly polar nature is unfavorable for oral absorption and/or penetration into the CNS. In the search for compounds with lower polarity than NBTI we replaced its ribose moiety by substituted benzyl groups. Halogen, hydroxyl, (trifluoro)methyl(-oxy), nitro, and amine functionalities were among the substituents at the benzyl group. In general, substitution of the benzyl group resulted in a lower affinity for ENT1. Only 2-hydroxyl substitution showed a higher affinity. Most likely this is the result of hydrogen bonding. Substitution at the 2-position of the benzyl group with aryl groups was also addressed. Compared to parent compound carrying a 2-phenylbenzyl group, all synthesized analogues gave higher affinities. Introduction of fluoro, trifluoromethyl, methoxy, and hydroxyl groups at the phenyl group clearly showed that addition to the 4-position was preferable. Despite the highly different character of a ribose and a benzyl group, K-i values in the low nanomolar range were obtained for the benzyl-substituted derivatives. Compound 35, LUF5919, and compound 60, LUF5929, displayed the highest affinity (K-i = 39 nM for both compounds), having a polar surface area of 101 Angstrom(2) and 85 Angstrom(2), respectively.

  DOI：

  10.1021/jm049735v

文献信息

• Inhibition of Nucleoside Transport by New Analogues of 4-Nitrobenzylthioinosine:  Replacement of the Ribose Moiety by Substituted Benzyl Groups
  作者：Reynier A. Tromp、Susan van Ameijde、Claudia Pütz、Corinna Sundermann、Bernd Sundermann、Jacobien K. von Frijtag Drabbe Künzel、Adriaan P. IJzerman

  DOI：10.1021/jm049735v

  日期：2004.10.1

  4-Nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside transport protein ENT1. However, its highly polar nature is unfavorable for oral absorption and/or penetration into the CNS. In the search for compounds with lower polarity than NBTI we replaced its ribose moiety by substituted benzyl groups. Halogen, hydroxyl, (trifluoro)methyl(-oxy), nitro, and amine functionalities were among the substituents at the benzyl group. In general, substitution of the benzyl group resulted in a lower affinity for ENT1. Only 2-hydroxyl substitution showed a higher affinity. Most likely this is the result of hydrogen bonding. Substitution at the 2-position of the benzyl group with aryl groups was also addressed. Compared to parent compound carrying a 2-phenylbenzyl group, all synthesized analogues gave higher affinities. Introduction of fluoro, trifluoromethyl, methoxy, and hydroxyl groups at the phenyl group clearly showed that addition to the 4-position was preferable. Despite the highly different character of a ribose and a benzyl group, K-i values in the low nanomolar range were obtained for the benzyl-substituted derivatives. Compound 35, LUF5919, and compound 60, LUF5929, displayed the highest affinity (K-i = 39 nM for both compounds), having a polar surface area of 101 Angstrom(2) and 85 Angstrom(2), respectively.