3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-hydroxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2(3H)-one | 933463-49-1

• 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-hydroxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2(3H)-one
• 英文别名: 3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-hydroxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one；3-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-6-(3-hydroxyphenyl)furo[2,3-d]pyrimidin-2(3H)-one；3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(3-hydroxyphenyl)furo[2,3-d]pyrimidin-2-one
• CAS: 933463-49-1
• 化学式: C₁₇H₁₆N₂O₆
• 分子量: 344.324
• InChiKey: HDOMTYGIAXABKT-NWANDNLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-hydroxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2(3H)-one 在 sodium hydroxide 过氧乙酸 、 磷酸 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以12%的产率得到3-(2'-deoxy-β-D-rybofuranosyl)-6-(3-hydroxy-4-<123I>iodopenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of an 123I-labeled bicyclic nucleoside analogue (BCNA) as potential SPECT tracer for VZV-tk reporter gene imaging

  摘要：

  An iodine-123 labeled bicyclic nucleoside analogue ([I-123]-4) has been synthesized and evaluated as a potential single photon emission tomography (SPECT) reporter probe for the non-invasive imaging of expression of the varicella zoster virus thymidine kinase (VZV-tk) reporter gene. In vitro enzymatic assays revealed that the non-radioactive mono-iodo derivative 4 has good affinity for VZV-TK (IC50: 4.2 mu M). Biodistribution of [I-123]-4 was examined in normal mice. Evaluation of [I-123]-4 in HEK-293T cells showed 1.74-fold higher accumulation in VZV-TK-expressing cells compared to control cells. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.081
• 作为产物：
  描述：

  碘苷 在 四(三苯基膦)钯 copper(l) iodide 、 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 23.0h， 生成 3-(2'-deoxy-β-D-ribofuranosyl)-6-(3-hydroxyphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2(3H)-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

• A <i>p</i>-[¹⁸F]Fluoroethoxyphenyl Bicyclic Nucleoside Analogue as a Potential Positron Emission Tomography Imaging Agent for Varicella-Zoster Virus Thymidine Kinase Gene Expression
  作者：Satish K. Chitneni、Christophe M. Deroose、Jan Balzarini、Rik Gijsbers、Sofie Celen、Zeger Debyser、Luc Mortelmans、Alfons M. Verbruggen、Guy M. Bormans

  DOI：10.1021/jm700971p

  日期：2007.12.27

  We recently reported a new positron emission tomography (PET) reporter gene, namely, varicella-zoster virus thymidine kinase (VZV-tk) in combination, with carbon-11 or fluorine-18 labeled m-alkoxyphenyl bicyclic nucleoside analogues (BCNAs) as PET reporter probes. We now report the synthesis and evaluation of p-alkoxyphenyl-BCNA tracers ([11C]-4 and [18F]-5), which are found to be superior to the m-alkoxyphenyl-BCNA

  我们最近报道了一个新的正电子发射断层扫描（PET）报告基因，即水痘-带状疱疹病毒胸苷激酶（VZV-tk）与碳11或氟18标记的间烷氧基苯基双环核苷类似物（BCNA）组合使用记者调查。现在，我们报告了对-烷氧基苯基-BCNA示踪剂的合成和评估（[11C] -4和[18F] -5），发现它们优于间烷氧基苯基-BCNA示踪剂。特别是，氟18标记的示踪剂（[18F] -5，IC50为4.2 microM）在VZV-tk表达细胞中比以前报道的间甲氧基苯基BCNA显示更高的积累。通过将苯酚前体3分别与作为烷基化剂的11CH 3I和18FCH 2CH 2Br加热来合成[11C] -4和[18F] -5。在293T细胞中对[11C] -4和[18F] -5进行的体外评估显示，其摄取量增加了约14倍和54倍，与对照细胞相比，它们分别进入了VZV-tk基因转导的细胞。LC-MS分析证实，VZV TK催化形成5