5'-O-(t-butyldimethylsilyl)-2',3'-O-isopropylidene-5-fluoro-6-carbaldehydeuridine | 1134188-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5'-O-(t-butyldimethylsilyl)-2',3'-O-isopropylidene-5-fluoro-6-carbaldehydeuridine
• 英文别名: 3-[(3aR,4R,6R,6aR)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-fluoro-2,6-dioxopyrimidine-4-carbaldehyde
• CAS: 1134188-93-4
• 化学式: C₁₉H₂₉FN₂O₇Si
• 分子量: 444.532
• InChiKey: MLRXXMXZQRSFMR-XKVFNRALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.93
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5'-O-(t-butyldimethylsilyl)-2',3'-O-isopropylidene-5-fluoro-6-carbaldehydeuridine 在 三氟乙酸 作用下， 以 水 为溶剂， 以88%的产率得到5-fluoro-6-carbaldehyde-uridine
  参考文献：
  名称：

  Structure−Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents

  摘要：

  A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations.

  DOI：

  10.1021/jm801224t
• 作为产物：
  描述：

  甲酸甲酯 、 5'-O-(tbutyldimethylsilyl)-2',3'-O-isopropylidene-5-fluorouridine 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以70%的产率得到5'-O-(t-butyldimethylsilyl)-2',3'-O-isopropylidene-5-fluoro-6-carbaldehydeuridine
  参考文献：
  名称：

  Structure−Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents

  摘要：

  A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations.

  DOI：

  10.1021/jm801224t

文献信息

• Structure−Activity Relationships of Orotidine-5′-Monophosphate Decarboxylase Inhibitors as Anticancer Agents
  作者：Angelica M. Bello、Danijela Konforte、Ewa Poduch、Caren Furlonger、Lianhu Wei、Yan Liu、Melissa Lewis、Emil F. Pai、Christopher J. Paige、Lakshmi P. Kotra

  DOI：10.1021/jm801224t

  日期：2009.3.26

  A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorouridine derivatives. The mononucleotide derivatives were used for enzyme inhibition investigations against ODCase. Anticancer activities of all the synthesized derivatives were evaluated using the nucleoside forms of the inhibitors. 5-Fluoro-UMP was a very weak inhibitor of ODCase. 6-Azido-5-fluoro and 5-fluoro-6-iodo derivatives are covalent inhibitors of ODCase, and the active site Lys145 residue covalently binds to the ligand after the elimination of the 6-substitution. Among the synthesized nucleoside derivatives, 6-azido-5-fluoro, 6-amino-5-fluoro, and 6-carbaldehyde-5-fluoro derivatives showed potent anticancer activities in cell-based assays against various leukemia cell lines. On the basis of the overall profile, 6-azido-5-fluoro and 6-amino-5-fluoro uridine derivatives exhibited potential for further investigations.