9-(2-benzoyloxyethoxymethyl)-purine | 75128-56-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 9-(2-benzoyloxyethoxymethyl)-purine
• 英文别名: 2-(Purin-9-ylmethoxy)ethyl benzoate
• CAS: 75128-56-2
• 化学式: C₁₅H₁₄N₄O₃
• 分子量: 298.301
• InChiKey: OSFLSGTXLQLYMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-(2-benzoyloxyethoxymethyl)-purine 在 甲胺 作用下， 反应 1.5h， 以28%的产率得到9-(2-羟基乙氧基甲基)-嘌呤
  参考文献：
  名称：

  Synthesis of analogs of l-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells

  摘要：

  L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepTl) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity Of L-valacyclovir for PepTl is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions Of L-valacyclovir with PepTl, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepTl in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety Of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepTl in binding studies, but only the purine analog (as the L-valine ester) showed PepT I-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepTl. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(02)00047-7
• 作为产物：
  描述：

  1-苯甲酰氧基-2-(氯甲氧基)乙烷 、 嘌呤 在 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.08h， 以28%的产率得到9-(2-benzoyloxyethoxymethyl)-purine
  参考文献：
  名称：

  Synthesis of analogs of l-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells

  摘要：

  L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepTl) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity Of L-valacyclovir for PepTl is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions Of L-valacyclovir with PepTl, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepTl in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety Of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepTl in binding studies, but only the purine analog (as the L-valine ester) showed PepT I-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepTl. (C) 2002 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(02)00047-7

文献信息

• Synthesis of analogs of l-valacyclovir and determination of their substrate activity for the oligopeptide transporter in Caco-2 cells
  作者：Gerda Marie Friedrichsen、Weiqing Chen、Mikael Begtrup、Chao-Pin Lee、Philip L Smith、Ronald T Borchardt

  DOI：10.1016/s0928-0987(02)00047-7

  日期：2002.7

  L-Valacyclovir, a prodrug of acyclovir, is a substrate for the peptide transporter (PepTl) in the intestinal mucosa, which accounts for its higher than expected oral bioavailability. The substrate activity Of L-valacyclovir for PepTl is surprising, particularly when one considers that the molecule has the structural features of a nucleoside rather than a peptide. In an attempt to better understand the structure-transport relationships (STR) for the interactions Of L-valacyclovir with PepTl, analogs of this molecule with structural changes in the guanine moiety were synthesized and their substrate activity for PepTl in Caco-2 cell monolayers was determined. The analogs synthesized include those that had the guanine moiety Of L-valacyclovir substituted with purine, benzimidazole, and 7-azaindole. All three analogs (purine, benzimidazole, and 7-azaindole) exhibited affinity for PepTl in binding studies, but only the purine analog (as the L-valine ester) showed PepT I-associated transcellular transport across Caco-2 cell monolayers. The benzimidazole and 7-azaindole analogs (as their L-valine esters) were rapidly metabolized by esterase when applied to the apical surface of Caco-2 cells, which probably explains their low penetration as the intact prodrugs via PepTl. (C) 2002 Elsevier Science B.V. All rights reserved.