5-iodo-3'-O-levulinyl-2'-deoxyuridine | 1146167-61-4

• 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-iodo-3'-O-levulinyl-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-oxopentanoate
• CAS: 1146167-61-4
• 化学式: C₁₄H₁₇IN₂O₇
• 分子量: 452.203
• InChiKey: BRNMEWXXOJBTIT-HBNTYKKESA-N

物化性质

• 熔点：
  164-166 °C
• 密度：
  1.81±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-iodo-3'-O-levulinyl-2'-deoxyuridine 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 5-iodo-5'-O-[cyclo-3,5-di(tert-butyl)-6-fluorosaligenyl]-2'-deoxyuridine monophosphate
  参考文献：
  名称：

  去甲肾上腺素转运蛋白靶向和DNA共同靶向的治疗性胍。

  摘要：

  即使采用积极治疗，高危神经母细胞瘤也经常复发。临床证据表明，增殖活动可预示不良预后。该报告描述了靶向去甲肾上腺素转运蛋白并经过细胞内加工的治疗性胍的合成，表征和生物学特性，随后将它们的分解代谢物有效地掺入了增殖性神经母细胞瘤细胞的DNA中。放射性胍是从5-radioiodo-2'-deoxyuridine（一种具有临床证明的最低毒性和DNA靶向特性的分子放射治疗平台）合成的。放射性胍转运到神经细胞瘤细胞是活性由细胞摄取的竞争抑制所指示的元-碘苄基胍。细胞内加工和DNA吸收的速率受试剂的分解代谢稳定性和细胞群体倍增时间的影响。放射毒性与DNA摄取量和暴露持续时间成正比。5- [ 125 I]碘-3'- O-（ε-胍基己酰基）-2'-脱氧尿苷在小鼠神经母细胞瘤模型中的生物分布显示出显着的肿瘤保留放射性。神经母细胞瘤异种移植物响应于该剂的临床上可达到的剂量而消退。

  DOI：

  10.1021/acs.jmedchem.9b00437
• 作为产物：
  描述：

  5-iodo-5'-O-trityl-3'-O-levulinyl-2'-deoxyuridine 在 氯化锆(IV) 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以78%的产率得到5-iodo-3'-O-levulinyl-2'-deoxyuridine
  参考文献：
  名称：

  [EN] MIBG ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE MIBG ET LEURS UTILISATIONS

  摘要：

  用于靶向表达去甲肾上腺素转运蛋白的细胞的化合物和组合物，以及制备和使用这些化合物的方法。这些化合物包括与活性药物结合的MIBG类似物，用于治疗和/或诊断各种疾病，包括神经母细胞瘤。

  公开号：

  WO2017053834A1

文献信息

• [EN] TARGETED RADIOLABELED COMPOUNDS AND THEIR USE FOR THE TREATMENT AND DIAGNOSIS OF CANCER<br/>[FR] COMPOSÉS RADIOMARQUÉS CIBLÉS, ET LEUR UTILISATION POUR LE TRAITEMENT ET LE DIAGNOSTIC DU CANCER
  申请人：UNIV NEBRASKA

  公开号：WO2011079245A1

  公开（公告）日：2011-06-30

  Method of using androgen receptor and/or butyrylcholinesterase targeted radiolabeled compounds, e.g., cycloSalingenyl pyrimidine nucleoside monophosphates, for the treatment and diagnosis of cancer.

  使用雄激素受体和/或丁酰胆碱酯酶靶向放射标记化合物的方法，例如环萨林基嘌呤核苷酸单磷酸，用于癌症的治疗和诊断。
• Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents
  申请人：Kortylewicz Zbigniew P.

  公开号：US20090117041A1

  公开（公告）日：2009-05-07

  Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

  本文披露了包含正电子发射体或伽马辐射放射性卤化物的某些环丝氨基嘧啶核苷酸单磷酸盐，其用于监测阿尔茨海默病的进展并评估对治疗的反应，以及它们的制备过程。
• MIBG analogs and uses thereof
  申请人：Board of Regents of The University of Nebraska

  公开号：US10874752B2

  公开（公告）日：2020-12-29

  Compounds and compositions for targeting cells expressing norepinephrine transporter, and methods of making and using the same. The compounds comprise MIBG analogs conjugated to active agents for treatment and/or diagnosis of various conditions, including neuroblastoma.

  用于靶向表达去甲肾上腺素转运体的细胞的化合物和组合物，以及制造和使用这些化合物和组合物的方法。这些化合物包括与活性剂共轭的 MIBG 类似物，用于治疗和/或诊断各种疾病，包括神经母细胞瘤。
• Radiolabeled 5-Iodo-3′-<i>O</i>-(17β-succinyl-5α-androstan-3-one)-2′-deoxyuridine and Its 5′-Monophosphate for Imaging and Therapy of Androgen Receptor-Positive Cancers: Synthesis and Biological Evaluation
  作者：Zbigniew P. Kortylewicz、Jessica Nearman、Janina Baranowska-Kortylewicz

  DOI：10.1021/jm9005803

  日期：2009.8.27

  High levels of androgen receptor (AR) are often indicative of recurrent, advanced, or metastatic cancers. These conditions are also characterized by a high proliferative fraction. 5-Radioiodo-3'-O-(17 beta-succinyl-5 alpha-androstan-3-one)-2'-deoxyuridine 8 and 5-radioiodo-3'-O-(17 beta-succinyl-5 alpha-androstan-3-one)-2'-deoxyuridin-5'-yl monophosphate 13 target AR. They are also degraded intracellularly to 5-radioiodo-2'-deoxyuridine 1 and its monophosphate 20. respectively, which can participate in the DNA synthesis. Both drugs were prepared at the no-carrier-added level. Precursors and methods are readily adaptable to radiolabeling with various radiohalides suitable for SPECT and PET imaging, its well as endoradiotherapy, In vitro and in vivo studies confirm the AR-dependent interactions. Both drugs bind to sex hormone binding globulin. This binding significantly improves their stability in serum. Biodistribution and imaging studies show preferential uptake and retention of 8 and 13 in ip xenografts of human ovarian adenocarcinoma cells NIH:OVCAR-3, which over express A R. When these drugs are administered at therapeutic dose levels, a significant tumor growth arrest is observed.
• Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation
  作者：Zbigniew P. Kortylewicz、Yu Kimura、Kotaro Inoue、Elizabeth Mack、Janina Baranowska-Kortylewicz

  DOI：10.1021/jm201482p

  日期：2012.3.22

  Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. 1050 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.