3'-O-(3-benzenesulfonylfuroxan-4-yl)-5-fluoro-2'-deoxyuridine

• 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: 3'-O-(3-benzenesulfonylfuroxan-4-yl)-5-fluoro-2'-deoxyuridine
• 英文别名: 1-[(2R,4S,5R)-4-[[4-(benzenesulfonyl)-5-oxido-1,2,5-oxadiazol-5-ium-3-yl]oxy]-5-(hydroxymethyl)oxolan-2-yl]-5-fluoropyrimidine-2,4-dione
• 化学式: C₁₇H₁₅FN₄O₉S
• 分子量: 470.392
• InChiKey: LJWSHOFTENEBPW-YNEHKIRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  182
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  5-氟-2'-脱氧脲核苷 在 咪唑 、 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3'-O-(3-benzenesulfonylfuroxan-4-yl)-5-fluoro-2'-deoxyuridine
  参考文献：
  名称：

  Design and Synthesis of 3‘- and 5‘-O-(3-Benzenesulfonylfuroxan-4-yl)-2‘-deoxyuridines:  Biological Evaluation as Hybrid Nitric Oxide Donor−Nucleoside Anticancer Agents

  摘要：

  A group of 3'-O- and 5'-O-(3-benzenesulfonylfuroxan-4-yl)-2'-deoxyuridines possessing a variety of substituents (H, Me, 1, F, CF3) at the C-5 position of the nucleoside moiety were synthesized for evaluation as hybrid anticancer agents that have the ability to simultaneously release cytotoxic nitric oxide ((NO)-N-.). Incubation of these nitric oxide donor-nucleoside conjugates in the presence of 18 MM L-cysteine released a high percentage of (NO)-N-. (21-48% at 1 h; 37-86% at 16 h). The release of (NO)-N-. in the absence of the thiol cofactor was negligible. These hybrid (NO)-N-. donor-nucleosides exhibited high cellular toxicity (CC50 = 10(-6)-10(-8) M range) against a battery of tumor cell lines (143B-LTK, 14313, EMT-6, KBALB-STK, and KBALB) and normal human fibroblasts (Hs578Bst). No differences in cytotoxicity between nontransfected (143B, KBALB) and the corresponding transfected (143B-LTK, KBALB-STK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK+) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect.

  DOI：

  10.1021/jm030544m

文献信息

• Design and Synthesis of 3‘- and 5‘-<i>O</i>-(3-Benzenesulfonylfuroxan-4-yl)-2‘-deoxyuridines:  Biological Evaluation as Hybrid Nitric Oxide Donor−Nucleoside Anticancer Agents
  作者：Sameh Moharram、Aihua Zhou、Leonard I. Wiebe、Edward E. Knaus

  DOI：10.1021/jm030544m

  日期：2004.3.1

  A group of 3'-O- and 5'-O-(3-benzenesulfonylfuroxan-4-yl)-2'-deoxyuridines possessing a variety of substituents (H, Me, 1, F, CF3) at the C-5 position of the nucleoside moiety were synthesized for evaluation as hybrid anticancer agents that have the ability to simultaneously release cytotoxic nitric oxide ((NO)-N-.). Incubation of these nitric oxide donor-nucleoside conjugates in the presence of 18 MM L-cysteine released a high percentage of (NO)-N-. (21-48% at 1 h; 37-86% at 16 h). The release of (NO)-N-. in the absence of the thiol cofactor was negligible. These hybrid (NO)-N-. donor-nucleosides exhibited high cellular toxicity (CC50 = 10(-6)-10(-8) M range) against a battery of tumor cell lines (143B-LTK, 14313, EMT-6, KBALB-STK, and KBALB) and normal human fibroblasts (Hs578Bst). No differences in cytotoxicity between nontransfected (143B, KBALB) and the corresponding transfected (143B-LTK, KBALB-STK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK+) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect.