5-(4-Fluoro-phenylethynyl)-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione | 151362-02-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-(4-Fluoro-phenylethynyl)-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione
• 英文别名: 5-[2-(4-fluorophenyl)ethynyl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 151362-02-6
• 化学式: C₁₇H₁₅FN₂O₅
• 分子量: 346.315
• InChiKey: FNGINWUFVMAGTI-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4-Fluoro-phenylethynyl)-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione 在 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 3-(2′-deoxy-β-D-ribofuranosyl)-6-(4-fluorophenyl)-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
• 作为产物：
  描述：

  (4-氟苯基乙炔)三甲基硅烷 在 四(三苯基膦)钯 氢氧化钾 、 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 5-(4-Fluoro-phenylethynyl)-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Palladium-catalyzed coupling of terminal alkynes with 5-(trifluoromethanesulfonyloxy)pyrimidine nucleosides

  摘要：

  The palladium-catalyzed couplings of terminal alkynes with 2',3',5'-tri-O-acetyl-5-(triflouromethanesulfonyloxy)uridine, 3',5'-di-O-acetyl-5-(triflouromethanesulfonyloxy)-2'-deoxyuridine, and 5-(triflouromethanesulfonyloxy)-2'-deoxyuridine have been investigated under a variety of conditions.

  DOI：

  10.1021/jo00076a019

文献信息

• Palladium-catalyzed coupling of terminal alkynes with 5-(trifluoromethanesulfonyloxy)pyrimidine nucleosides
  作者：Geoffrey T. Crisp、Bernard L. Flynn

  DOI：10.1021/jo00076a019

  日期：1993.11

  The palladium-catalyzed couplings of terminal alkynes with 2',3',5'-tri-O-acetyl-5-(triflouromethanesulfonyloxy)uridine, 3',5'-di-O-acetyl-5-(triflouromethanesulfonyloxy)-2'-deoxyuridine, and 5-(triflouromethanesulfonyloxy)-2'-deoxyuridine have been investigated under a variety of conditions.
• 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.