5-iodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridine | 848318-65-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 5-iodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridine
• 英文别名: 1-O-[(5S,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl] 4-O-[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-iodo-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] butanedioate
• CAS: 848318-65-0
• 化学式: C₃₂H₄₃IN₂O₉
• 分子量: 726.606
• InChiKey: RDGHZEHHGPDTHJ-MZKWEORMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  149
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-iodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridine 、 六甲基二锡 在 钯 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-trimethylstannyl-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridine
  参考文献：
  名称：

  Cancer specific radiolabeled conjugates regulated by the cell cycle for the treatment and diagnosis of cancer

  摘要：

  揭示了具有一种有效靶向肿瘤细胞的成分的放射性标记结合物，这些细胞选择性地吸收和降解结合物，从而将能够被核物质吸收的放射性同位素传递至肿瘤细胞核，以产生细胞毒作用和/或使细胞可通过放射成像检测。

  公开号：

  US20050069495A1
• 作为产物：
  描述：

  5'-DMT-protected 6 在 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 4.0h， 以82%的产率得到5-iodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridine
  参考文献：
  名称：

  Cancer specific radiolabeled conjugates regulated by the cell cycle for the treatment and diagnosis of cancer

  摘要：

  揭示了具有一种有效靶向肿瘤细胞的成分的放射性标记结合物，这些细胞选择性地吸收和降解结合物，从而将能够被核物质吸收的放射性同位素传递至肿瘤细胞核，以产生细胞毒作用和/或使细胞可通过放射成像检测。

  公开号：

  US20050069495A1

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.