(E)-5-(2-iodovinyl)-2'-ribofluoro-2'-deoxyuridine | 121563-65-3

• 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: (E)-5-(2-iodovinyl)-2'-ribofluoro-2'-deoxyuridine
• 英文别名: 1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[(E)-2-iodoethenyl]pyrimidine-2,4-dione
• CAS: 121563-65-3
• 化学式: C₁₁H₁₂FIN₂O₅
• 分子量: 398.13
• InChiKey: PZPQPNSQTAMTEX-YPLKXGEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 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：

  (E)-5-(2-iodovinyl)-2'-ribofluoro-2'-deoxyuridine 在 吡啶 、 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (E)-5-(2-iodovinyl)-2'-fluoro-3'-O-(3-pyridylcarbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis of (E)-5-(2-cIOdovinyl)-3′-0-(1-Methyl-1,4-Dihydropyridyl-3 -Carbonyl)-2′-Fluoro-2′-Deoxyuridine (Ivfru-Cds) for Brain Targetted Delivery of Ivfru, an Antiviral Nucleoside

  摘要：

  （E）-5-（2-洛德维）-2'-含氟-3'-O-（1-甲基-1,4-二氢吡啶-3-羰基）-2'-脱氧尿idine（11）被制备出来，作为未来评估一种脂溶性、中枢神经系统选择性、吡rido素降磷酸酶鲁棒、抗病毒药物治疗单纯型小细胞热 herpesis 的可能候选药物。在 DMF 溶液中加入 TBDMSHCl 并加入imidazole，6 号化合物（E）-5-（2-碘维）-2'-含氟-2'-脱氧尿idine通过反应获得保护的 5'-O-t-butyldimethylsilyl 通的道路（7）。随后，与对氯尼古丁酸在吡咯中反应，得到（E）-5-（2-碘维）-2'-含氟-3'-O-（3-吡咯羰基）-5'-O-t-butyldimethylsilyl-2'-脱氧尿idine（8）。通过使用 n-Bu4N 和 F- 处理，清除 8 号的硅醚基团，并以碘甲烷对生成的 3'-O-（3-吡咯羰基）产物进行 quaternization，得到 9 号的对应 1-甲基吡咯阳离子（10）。后者被利用亚硫酸亚离子还原得到（E）-5-（2-碘维）-2'-含氟-3'-O-（1-甲基-1,4-二氢吡咯-3-羰基）-2'-脱氧尿idine（11）。

  DOI：

  10.1080/07328319308018560
• 作为产物：
  描述：

  5-iodo-2'-deoxy-2'-fluorouridine 在 bis-triphenylphosphine-palladium(II) chloride 、 一氯化碘 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 16.5h， 生成 (E)-5-(2-iodovinyl)-2'-ribofluoro-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis and Cellular Uptake of 2‘-Substituted Analogues of (E)-5-(2-[¹²⁵I]Iodovinyl)-2‘-deoxyuridine in Tumor Cells Transduced with the Herpes Simplex Type-1 Thymidine Kinase Gene. Evaluation as Probes for Monitoring Gene Therapy

  摘要：

  A useful synthetic methodology was developed to synthesize and radiolabel a series of (E)-5-(2-[I-125]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (HSV-1 TK). (E)-5-(2-[I-125]Iodovinyl)-2'-deoxyuridine ([I-125]IVDU, 10), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyuridine ([I-125]IVFRU, 11), (E)-5-(2-[I-125]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([I-125]IVFAU, 12), and (E)-5-(2-[I-125]iodovinyl)arabinouridine ([I-125]IVAU, 13) were synthesized in 63-83% radiochemical yield by reaction of the unprotected (E)-5-(2-(trimethylsilyl)vinyl) precursors (6-9) with [I-125]ICl. Cellular uptake of these labeled compounds (10-13) was evaluated in vitro. All compounds showed minimal uptake in the KBALB cell line. However, increased uptake was observed for all compounds in KBALB-STK cells which are transduced with a replication incompetent Moloney murine leukemia virus vector encoding the HSV-1 TK gene. The results indicate that uptake of these compounds in KBALB-STK cells is variable and highly dependent on the nature of the sugar 2'-substituent. When a fluoro (12) or a hydroxy (13) substituent is present in the arabinofuranosyl (up) configuration at the 2'-position, there is diminished cellular uptake in KBALB-STK cells relative to hydrogen (10) or fluorine (11) in the ribofuranosyl (down) configuration at the 2'-position. Our results indicate that radiolabeled IVFRU (11) is most promising for further in vivo studies.

  DOI：

  10.1021/jm9606406

文献信息

• Combined use of nucleoside analogues and gene transfection for tissue imaging and therapy
  申请人：——

  公开号：US20020025296A1

  公开（公告）日：2002-02-28

  A method and use of a labelled compound for monitoring the transfer of a foreign gene including selecting the foreign gene which has been isolated from a cell or virus and transferred into a cell population and selecting the labelled compound which will interact selectively with a protein expressed by the foreign gene to produce a labelled product. The labelled compound has a rate of expulsion from the cells which is greater than that of the labelled product. Further, the use and method include administering to the cells an effective dose of the labelled compound such that the labelled compound selectively interacts with the protein to produce the labelled product, waiting a period of time such that a substantial amount of the labelled compound has been expelled from the cells and such that a detectable amount of the labelled product remains and determining the extent and location of the protein by detecting the labelled product.

  一种使用标记化合物监测外源基因转移的方法和用途，包括选择已从细胞或病毒中分离并转移到细胞群体中的外源基因和选择将与外源基因表达的蛋白质选择性相互作用以产生标记产物的标记化合物。标记化合物从细胞中排出的速率大于标记产物。此外，该使用和方法包括向细胞施加有效剂量的标记化合物，使标记化合物选择性地与蛋白质相互作用以产生标记产物，等待一段时间，使大量标记化合物已经排出细胞且仍有可检测量的标记产物，并通过检测标记产物确定蛋白质的程度和位置。
• RECOMBINANT VACCINIA VIRUS AND METHODS OF USE THEREOF
  申请人：Ignite Immunotherapy, Inc.

  公开号：EP3923967A1

  公开（公告）日：2021-12-22
• [EN] NON-INVASIVE IMAGING OF GENE TRANSFER<br/>[FR] IMAGERIE DE TRANSFERT GENIQUE NON EFFRACTIVE
  申请人：SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH

  公开号：WO1996028190A1

  公开（公告）日：1996-09-19

  (EN) The subject invention provides a method of detecting gene transfer to and expression in a target tissue of a host subject comprising: (a) administering to the host subject a transfer vector containing a marker gene not naturally present in the host and non-toxic to the host, wherein the transfer vector transfects cells of the target tissue, under condition such that the marker gene is expressed in transfected cells of the target tissue, thereby generating marker gene product; (b) administering to the host subject a labelled marker substrate which is not metabolized by non-transfected cells, under conditions such that the marker substrate is metabolized by the marker gene product of step (a) to produce a labelled marker metabolite which is substantially retained in the transfected cells throughout a time-period sufficient for imaging the labelled marker metabolite, and (c) imaging the labelled marker metabolite, thereby detecting gene transfer to and expression in the target tissue. The subject invention provides a non-invasive, clinically applicable method for imaging gene transfer and expression which can be implemented using existing imaging techniques to monitor and evaluate $i(in vivo) gene therapy in human subjects.(FR) Cette invention concerne un procédé permettant de détecter le transfert génique vers un tissu cible d'un sujet hôte, ainsi que l'expression génique dans ce même tissu. Ce procédé comprend les étapes suivantes: a) administration au sujet hôte d'un vecteur de transfert contenant un gène de marquage n'étant pas présent naturellement chez ce dernier et n'étant pas toxique pour lui, lequel vecteur transfecte les cellules du tissu cible dans des conditions telles que le gène de marquage soit exprimé dans les cellules transfectées du tissu cible afin d'obtenir un produit de gène de marquage; b) administration au sujet hôte d'un substrat de marquage marqué ne pouvant être métabolisé par les cellules non transfectées, et ceci dans des conditions telles que le substrat de marquage soit métabolisé par le produit du gène de marquage obtenu en a) afin d'obtenir un métabolite de marquage marqué qui puisse être sensiblement retenu par les cellules transfectées pendant une période suffisante pour en obtenir une image; et c) affichage de l'image dudit métabolite de marquage marqué afin de pouvoir détecter le transfert génique vers le tissu cible ainsi que l'expression génique dans ce dernier. La présente invention propose un procédé non effractif et applicable cliniquement qui permet d'obtenir une image du transfert et de l'expression géniques, lequel procédé peut être mis en ÷uvre au moyen des techniques d'imagerie pour le contrôle et l'évaluation de la thérapie génique $i(in vivo) chez des sujets humains.
• [EN] RECOMBINANT VACCINIA VIRUS AND METHODS OF USE THEREOF<br/>[FR] VIRUS DE LA VACCINE RECOMBINANT ET SES PROCÉDÉS D'UTILISATION
  申请人：IGNITE IMMUNOTHERAPY INC

  公开号：WO2020165730A1

  公开（公告）日：2020-08-20

  The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus, compositions comprising the vaccinia virus, and use of the vaccinia virus or composition for inducing oncolysis in an individual having a tumor.
• Synthesis of (<i>E</i>)-5-(2-cIOdovinyl)-3′-0-(1-Methyl-1,4-Dihydropyridyl-3 -Carbonyl)-2′-Fluoro-2′-Deoxyuridine (Ivfru-Cds) for Brain Targetted Delivery of Ivfru, an Antiviral Nucleoside
  作者：Rakesh Kumar、Edward E. Knaus、Leonard I. Wiebe

  DOI：10.1080/07328319308018560

  日期：1993.11

  (E)-5-(2-lodovinyl)-2'-fluoro-3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (11) was synthesized for future evaluation as a lipophilic, brain-selective, pyrimidine phosphorylase-resistant, antiviral agent for the treatment of Herpes simplex encephalitis (HSE). Treatment of (E)-5-(2-iodovinyl)-2'-fluoro-2'-deoxyuridine (6) with TBDMSCl in the presence of imidazole in DMF yielded the protected 5'-O-t-butyldimethylsilyl derivative (7). Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded (E)-5-(2-iodovinyl)-2'-fluoro-3'-O-(3-pyridylcarbonyl)-5'-O-t-butyldimethylsilyl-2'-deoxyuridine (8). Deprotection of the silyl ether moiety of 8 with n-Bu4N + F- and quaternization of the resulting 3'-O-(3-pyridylcarbonyl) derivative 9 using iodomethane afforded the corresponding 1-methylpyridinium salt 10. The latter was reduced with sodium dithionite to yield (E)-5-(2-iodovinyl)-2'-fluoro-3'-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2'-deoxyuridine (11).

  （E）-5-（2-洛德维）-2'-含氟-3'-O-（1-甲基-1,4-二氢吡啶-3-羰基）-2'-脱氧尿idine（11）被制备出来，作为未来评估一种脂溶性、中枢神经系统选择性、吡rido素降磷酸酶鲁棒、抗病毒药物治疗单纯型小细胞热 herpesis 的可能候选药物。在 DMF 溶液中加入 TBDMSHCl 并加入imidazole，6 号化合物（E）-5-（2-碘维）-2'-含氟-2'-脱氧尿idine通过反应获得保护的 5'-O-t-butyldimethylsilyl 通的道路（7）。随后，与对氯尼古丁酸在吡咯中反应，得到（E）-5-（2-碘维）-2'-含氟-3'-O-（3-吡咯羰基）-5'-O-t-butyldimethylsilyl-2'-脱氧尿idine（8）。通过使用 n-Bu4N 和 F- 处理，清除 8 号的硅醚基团，并以碘甲烷对生成的 3'-O-（3-吡咯羰基）产物进行 quaternization，得到 9 号的对应 1-甲基吡咯阳离子（10）。后者被利用亚硫酸亚离子还原得到（E）-5-（2-碘维）-2'-含氟-3'-O-（1-甲基-1,4-二氢吡咯-3-羰基）-2'-脱氧尿idine（11）。