5-iodo-3'-O-succinyl-2'-deoxyuridine ethyl ester | 1182735-52-9

• 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-succinyl-2'-deoxyuridine ethyl ester
• 英文别名: 1-O-ethyl 4-O-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] butanedioate
• CAS: 1182735-52-9
• 化学式: C₁₅H₁₉IN₂O₈
• 分子量: 482.229
• InChiKey: UHBGEZFRJRDJQZ-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 水 、 三氟乙酸 作用下， 以 叔丁醇 为溶剂， 反应 2.0h， 以0.42 g的产率得到5-iodo-3'-O-succinyl-2'-deoxyuridine ethyl ester
  参考文献：
  名称：

  Radiolabeled 5-Iodo-3′-O-(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

  摘要：

  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.

  DOI：

  10.1021/jm9005803