1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-iodouracil | 157428-24-5

• 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: 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-iodouracil
• 英文别名: 3-N-benzoyl-3',5'-di-O-benzoyl-2'-fluoro-2'-deoxy-5-iodo-1-β-D-arabinouridine；3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine；[(2R,3R,4S,5R)-5-(3-benzoyl-5-iodo-2,4-dioxopyrimidin-1-yl)-3-benzoyloxy-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 157428-24-5
• 化学式: C₃₀H₂₂FIN₂O₈
• 分子量: 684.416
• InChiKey: WDCNMARBDPUEPH-JPYYHWIRSA-N

物化性质

• 沸点：
  715.8±70.0 °C(predicted)
• 密度：
  1.70±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-iodouracil 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-ethynyluracil
  参考文献：
  名称：

  Synthesis and Biological Properties of5-o-Carboranyl-1-(2-deoxy-2-fluoro-.beta.-D-arabinofuranosyl)uracil

  摘要：

  A novel 5-o-carboranyl-containing nucleoside, 5-o-carboranyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)urac il (6, CFAU), was synthesized as a potential intracellular neutron capture agent. This compound was prepared in five steps starting from 5-iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (1). The desired carboranyl derivative was obtained by addition of decaborane [as the bis(propionitrile) adduct] to the protected acetylenic nucleoside precursor followed by debenzoylation. The synthesis of CFAU was also performed by glycosylation of the suitably protected 5-o-carboranyluracil with the appropriate 2-fluoroarabinosyl derivative. This compound was evaluated for its cytotoxicity in human lymphocytes, monkey cells, and rat and human gliomas cells, as well as for antiviral activity against human immunodeficiency virus and herpes simplex virus type 1. Its biological activity was compared to 5-o-carboranyl-1-(2-deoxyribofuranosyl)uracil in these cell culture systems, human bone marrow cells, and mice. The results obtained to date suggest that CFAU has suitable characteristics as a sensitizer for boron neutron capture therapy.

  DOI：

  10.1021/jm00042a011
• 作为产物：
  描述：

  苯甲酰氯 、 非阿尿苷 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 34.0h， 以91%的产率得到1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)-N³-benzoyl-5-iodouracil
  参考文献：
  名称：

  Synthesis of 5-Fluoroalkylated Pyrimidine Nucleosides via Negishi Cross-Coupling

  摘要：

  5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.

  DOI：

  10.1021/jo800444y

文献信息

• Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression
  作者：Ann-Marie Chacko、Wenchao Qu、Hank F. Kung

  DOI：10.1021/jm800501d

  日期：2008.9.25

  Two novel series of 5-fluoroalkyl-2'-deoxyuridines (FPrDU, FBuDU, FPeDU) and 2'-fluoro-2'-deoxy-5-fluoroalkylarabinouridines (FFPrAU, FFBuAU, FFPeAU) that have three, four, or five methylene units (propyl, butyl, or pentyl) at C-5 were prepared and tested as reporter probes for imaging herpes simplex virus type I thymidine kinase (HSV1-tk) gene expression. The Negishi coupling methodology was employed in efficiently synthesizing the radiolabeling precursors. All six 5-[F-18]fluoroalkyl pyrimidines were readily prepared from 3-N-benzoyl-3',5'-di-O-benzoyl-protected 5-O-mesylate Precursors in 17-35% radiochemical yield (decay-corrected). In vitro studies highlighted that all six [F-18]-labeled nucleosides selectively accumulated in cells expressing the HSV1-TK protein and there was negligible uptake in control cells. [F-18]FPrDU, [F-18]FBuDU, [F-18]FPeDU, and [F-18]FFBuAU had the best uptake profiles. Despite their selective accumulation in HSV1-tk-expressing cells, all 5-fluoroalkyl pyrimidine nucleosides had low-to-negligible cytotoxic activity (CC50 > 1000-1209 mu M). Ultimately, the results demonstrated that 5-[F-18]fluoropropyl, [F-18]fluorobutyl, and [F-18]fluoropentyl pyrimidine nucleosides have the potential to be in vivo HSV1-TK PET reporter probes over a dynamic range of reporter gene expression levels.
• EP0788364A4
  申请人：——

  公开号：EP0788364A4

  公开（公告）日：1998-05-06
• TREATMENT OF UROGENITAL CANCER WITH BORON NEUTRON CAPTURE THERAPY
  申请人：EMORY UNIVERSITY

  公开号：EP0788364A1

  公开（公告）日：1997-08-13
• [EN] TREATMENT OF UROGENITAL CANCER WITH BORON NEUTRON CAPTURE THERAPY<br/>[FR] TRAITEMENT DE CANCERS UROGENITAUX PAR THERAPIE AU BORE ET A CAPTURE DE NEUTRONS
  申请人：EMORY UNIVERSITY

  公开号：WO1996014073A1

  公开（公告）日：1996-05-17

  (EN) Methods and compositions for treating urogenital tumors, and in particular, cancer of the prostate, bladder, and kidney, with BCNT, are disclosed. Any boron-containing compound that is sufficiently lipophilic to pass through the appropriate urogenital membranes in a quantity high enough to achieve therapy on irradiation with low-energy neutrons can be used. Carboranyl-containing nucleosides and oligonucleotides are particularly suited for use in BNCT of urogenital tumors. Preferred compounds include 5-carboranyl-2'-deoxyuridine (CDU) and 5-o-carboranyl-1-(2-deoxy-2-fluoro-$g(b)-D-arabinofuranosyl)uracil (CFAU). Nucleosides and oligonucleotides bearing an -O-[(carboran-1-yl)alkyl]phosphate, S-[(carboran-1-yl)alkyl]phosphorothioate, or Se-[(carboran-1-yl)alkyl]phosphoroselenoate in place of the (carboran-1-yl)phosphonate moiety can be used. Oligonucleotides of specific gene sequences that include one or more 3', 5'-linking-(carboran-1-yl)phosphonate moieties can also be used in antisense therapy in the selective modification of gene expression. Compounds can be used in urogenital BNCT therapy that contain boron clusters as a means to enhance lipophilicity wherein the boron is not enriched in 10B, but instead, in the 11B isotope. The therapy is accomplished by administering the boron-containing compound by any appropriate route, including by intravenous injection, oral delivery or by catheter or other direct means, in such a manner that the compound accumulates in the target tumor. After desired accumulation of the compound in the tumor, the site is irradiated with an effective amount of low energy neutrons.(FR) On décrit des procédés et compositions de traitement de tumeurs urogénitales et en particulier de cancers de la prostate, de la vessie et des reins, par BNCT (thérapie au bore et à capture de neutrons). On peut utiliser tout composé, contenant du bore, qui est assez lipophile pour traverser les membranes urogénitales appropriées en quantité suffisante pour produire un effet thérapeutique lors de l'irradiation avec des neutrons à basse énergie. Des nucléosides et oligonucléotides contenant du carboranyle conviennent particulièrement pour une utilisation dans une BNCT de tumeurs urogénitales. Les composés preférés incluent 5-carboranyl-2'-déoxyuridine (CDU) et 5-o-carboranyl-1-(2-désoxy-2-fluoro-$g(b)-D-arabinofuranosyl)uracile (CFAU). Des nucléosides et oligonucléotides portant -O-[(carbora-1-yl)alkyl]phosphate, S-[(carborane-1-yl)alkyl]phosphorothioate, ou Se-[(carborane-1-yl)alkyl]phosphorosélénoate à la place de la fraction (carbone-1-yl)phosphonate peuvent être utilisés. Des oligonucléotides à sequences de gènes spécifiques qui comprennent une ou plusieurs fractions (carborane-1-yle)phosphonate se liant en 3',5' peuvent aussi servir dans une thérapie antisens pour la modification sélective de l'expression génique. On peut utiliser pour une BNCT urogénitale des composés qui contiennent des amas de bore pour améliorer leur lipophilie, ce bore n'étant pas enrichi en B10 mais en l'isotope B11. Cette thérapie consiste à administrer le composé contenant du bore par toute voie appropriée, y compris par injection intraveineuse, par voie orale ou par cathéter ou tout autre moyen direct, de façon que les composés s'accumulent dans la tumeur cible en quantité souhaitée, puis à irradier le site avec une quantité efficace de neutrons à faible énergie.