5-iodo-5'-O-trityl-3'-O-levulinyl-2'-deoxyuridine | 1209526-88-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5-iodo-5'-O-trityl-3'-O-levulinyl-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] 4-oxopentanoate
• CAS: 1209526-88-4
• 化学式: C₃₅H₃₅IN₂O₉
• 分子量: 754.575
• InChiKey: IFPURBRVEBPYTL-OJDZSJEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  47
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  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：

  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：

  碘苷 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 5-iodo-5'-O-trityl-3'-O-levulinyl-2'-deoxyuridine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm201482p

文献信息

• 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.