[2-amino-9-(2-hydroxyethoxymethyl)-9H-purin-6-yloxy]acetic acid ethyl ester

• 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: [2-amino-9-(2-hydroxyethoxymethyl)-9H-purin-6-yloxy]acetic acid ethyl ester
• 英文别名: Ethyl 2-[2-amino-9-(2-hydroxyethoxymethyl)purin-6-yl]oxyacetate
• 化学式: C₁₂H₁₇N₅O₅
• 分子量: 311.297
• InChiKey: URMVQUTZNVWHSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  阿昔洛韦 在 三乙烯二胺 、 咪唑 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 57.5h， 生成 [2-amino-9-(2-hydroxyethoxymethyl)-9H-purin-6-yloxy]acetic acid ethyl ester
  参考文献：
  名称：

  Polar, functionalized guanine-O6 derivatives resistant to repair by O6-alkylguanine–DNA alkyltransferase: implications for the design of DNA-modifying drugs

  摘要：

  The protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the repair of DNA lesions generated by several clinically important anti-cancer drugs; this is manifest as active resistance in those cancer cell lines proficient in Atase expression. Novel O6-substituted guanine analogues have been synthesized, bearing acidic, basic and hydrogen bonding functional groups. In contrast to existing O6-modified purine analogues, such as methyl or benzyl, the new compounds were found to resist repair by Atase even when tested at concentrations much higher than O6-benzylguanine, a well-established Atase substrate active both in vitro and in vivo. The inactivity of the new purines as covalent substrates for Atase indicates that agents to deliver these groups to DNA would represent a new class of DNA-modifying drug that circumvents Atase-mediated resistance. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2005.11.007

文献信息

• Polar, functionalized guanine-O6 derivatives resistant to repair by O6-alkylguanine–DNA alkyltransferase: implications for the design of DNA-modifying drugs
  作者：Dimitrios Pletsas、Richard T. Wheelhouse、Vassiliki Pletsa、Anna Nicolaou、Terence C. Jenkins、Michael C. Bibby、Soterios A. Kyrtopoulos

  DOI：10.1016/j.ejmech.2005.11.007

  日期：2006.3

  The protein O6-alkylguanine-DNA alkyltransferase (Atase) is responsible for the repair of DNA lesions generated by several clinically important anti-cancer drugs; this is manifest as active resistance in those cancer cell lines proficient in Atase expression. Novel O6-substituted guanine analogues have been synthesized, bearing acidic, basic and hydrogen bonding functional groups. In contrast to existing O6-modified purine analogues, such as methyl or benzyl, the new compounds were found to resist repair by Atase even when tested at concentrations much higher than O6-benzylguanine, a well-established Atase substrate active both in vitro and in vivo. The inactivity of the new purines as covalent substrates for Atase indicates that agents to deliver these groups to DNA would represent a new class of DNA-modifying drug that circumvents Atase-mediated resistance. (c) 2006 Elsevier SAS. All rights reserved.