3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
• 英文别名: 6-[3-(2-fluoroethoxy)phenyl]-3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]furo[2,3-d]pyrimidin-2-one
• 化学式: C₁₉H₁₉FN₂O₆
• 分子量: 390.368
• InChiKey: KQLFOIAXOLHCMZ-USXIJHARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  碘苷 在 四(三苯基膦)钯 copper(l) iodide 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation of ¹⁸F- or ¹¹C-Labeled Bicyclic Nucleoside Analogues as Potential Probes for Imaging Varicella-Zoster Virus Thymidine Kinase Gene Expression Using Positron Emission Tomography

  摘要：

  Two radiolabeled bicyclic nucleoside analogues (BCNAs) were synthesized, namely 3-(2'-deoxy-beta-d-ribofuranosyl)-6-(3-[F-18]fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([F-18]-2) and 3-(2'-deoxy-beta-d-ribofuranosyl)-6-(3-[C-11]methoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([C-11]-3), and evaluated as PET reporter probes for varicella-zoster virus thymidine kinase (VZV-tk) gene expression imaging in brain. [F-18]-2 and [C-11]-3 were synthesized starting from phenol precursor 1. The phenol precursor 1 was converted to stable as well as to radiolabeled compounds 2 and 3 using (FCH2CH2Br)-F-19/18 or (CH3I)-C-12/11 as alkylating agent. In vitro evaluation of [F-18]-2 and [C-11]-3 in 293T cells showed a 4.5 and 53-fold higher uptake, respectively, into VZV-tk gene-transduced cells compared to control cells. However, biodistribution studies in mice demonstrated low uptake of these tracers in the brain. RP-HPLC analysis of plasma and urine samples of mice injected with [C-11]-3 revealed that this tracer is very stable in vivo. These data warrant further evaluation of these tracers as noninvasive imaging agents for VZV infection and VZV-tk reporter gene expression in vivo.

  DOI：

  10.1021/jm060964m

文献信息

• Synthesis and Preliminary Evaluation of ¹⁸F- or ¹¹C-Labeled Bicyclic Nucleoside Analogues as Potential Probes for Imaging Varicella-Zoster Virus Thymidine Kinase Gene Expression Using Positron Emission Tomography
  作者：Satish K. Chitneni、Christophe M. Deroose、Jan Balzarini、Rik Gijsbers、Sofie J. L. Celen、Tjibbe J. de Groot、Zeger Debyser、Luc Mortelmans、Alfons M. Verbruggen、Guy M. Bormans

  DOI：10.1021/jm060964m

  日期：2007.3.1

  Two radiolabeled bicyclic nucleoside analogues (BCNAs) were synthesized, namely 3-(2'-deoxy-beta-d-ribofuranosyl)-6-(3-[F-18]fluoroethoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([F-18]-2) and 3-(2'-deoxy-beta-d-ribofuranosyl)-6-(3-[C-11]methoxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one ([C-11]-3), and evaluated as PET reporter probes for varicella-zoster virus thymidine kinase (VZV-tk) gene expression imaging in brain. [F-18]-2 and [C-11]-3 were synthesized starting from phenol precursor 1. The phenol precursor 1 was converted to stable as well as to radiolabeled compounds 2 and 3 using (FCH2CH2Br)-F-19/18 or (CH3I)-C-12/11 as alkylating agent. In vitro evaluation of [F-18]-2 and [C-11]-3 in 293T cells showed a 4.5 and 53-fold higher uptake, respectively, into VZV-tk gene-transduced cells compared to control cells. However, biodistribution studies in mice demonstrated low uptake of these tracers in the brain. RP-HPLC analysis of plasma and urine samples of mice injected with [C-11]-3 revealed that this tracer is very stable in vivo. These data warrant further evaluation of these tracers as noninvasive imaging agents for VZV infection and VZV-tk reporter gene expression in vivo.