9-(2-羟基乙氧基甲基)-嘌呤 | 1025910-00-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 9-(2-羟基乙氧基甲基)-嘌呤
• 英文名称: 9-(2-hydroxyethoxymethyl)-purine
• 英文别名: 2-(Purin-9-ylmethoxy)ethanol
• CAS: 1025910-00-2
• 化学式: C₈H₁₀N₄O₂
• 分子量: 194.193
• InChiKey: MIQAYYADYWRRMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-(2-羟基乙氧基甲基)-嘌呤 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成 2-(9-purinemethoxy)ethyl-L-valinate
  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：

  嘌呤 在 甲胺 、 lithium diisopropyl amide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 27.58h， 生成 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

文献信息

• PROCESS OF PREPARATION OF VALACYCLOVIR AND RELEVANT INTERMEDIATES
  申请人：INDUSTRIALE CHIMICA S.r.l.

  公开号：EP0915874B1

  公开（公告）日：2003-12-10
• EP0804547A4
  申请人：——

  公开号：EP0804547A4

  公开（公告）日：1999-11-03
• UNIQUE ASSOCIATED KAPOSI'S SARCOMA VIRUS SEQUENCES AND USES THEREOF
  申请人：The Trustees of Columbia University in the City of New York

  公开号：EP0804547A1

  公开（公告）日：1997-11-05
• [EN] PROCESS OF PREPARATION OF VALACYCLOVIR AND RELEVANT INTERMEDIATES<br/>[FR] PROCEDE DE PREPARATION DE VALACYCLOVIR ET DE PRODUITS INTERMEDIAIRES PRESENTANT UN INTERET PARTICULIER
  申请人：——

  公开号：WO1998003553A1

  公开（公告）日：1998-01-29

  [EN] Process of preparation of valacyclovir (I), wherein derivative (IV) of acyclovir (I), in which the OH group of acyclovir at the omega position has been replaced by a good leaving group Z, is reacted with an alkaline salt of L-valine (V), to give intermediate (VI), which is successively hydrolyzed in an acid medium to give the corresponding salified valacyclovir (I-A), which may be optionally transformed into valacyclovir (I).
  [FR] Cette invention concerne un procédé de préparation de valacyclovir (I), lequel fait appel à un dérivé (IV) d'acyclovir (I) dans lequel le groupe OH de l'acyclovir a été remplacé à la position oméga par un groupe partant Z viable. Ce procédé consiste à faire réagir le dérivé avec un sel alcalin de L-valine (V) de manière à obtenir un produit intermédiaire (VI). Ce produit peut ensuite être hydrolysé dans un milieu acide afin de produire le valacyclovir salifié (I-A) correspondant, ce dernier pouvant éventuellement être transformé en valacyclovir (I).
• 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.