[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(E)-4-[tert-butyl(diphenyl)silyl]oxybut-2-enyl] carbonate | 362513-93-7

• 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: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(E)-4-[tert-butyl(diphenyl)silyl]oxybut-2-enyl] carbonate
• CAS: 362513-93-7
• 化学式: C₃₁H₃₇N₅O₇Si
• 分子量: 619.75
• InChiKey: AVGCORZUSIEENA-MAGPYODBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(E)-4-[tert-butyl(diphenyl)silyl]oxybut-2-enyl] carbonate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以85%的产率得到Carbonic acid (2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester (E)-4-hydroxy-but-2-enyl ester
  参考文献：
  名称：

  New 3‘-Azido-3‘-deoxythymidin-5‘-yl O-(4-Hydroxyalkyl or -Alkenyl or -Alkylepoxide) Carbonate Prodrugs:  Synthesis and Anti-HIV Evaluation

  摘要：

  New 5 ' -O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5 ' -O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement was confirmed by comparison of the serum half-lives of the 3 ' -azido-3 ' -deoxythymidin-5 ' -yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs with our thermodynamic predictions. Interestingly, these 5 ' -O-carbonate prodrug series show increased anti-HIV potencies in conjunction with, or without, reduced cytotoxicity as compared to AZT that lead to a gain in selectivity indexes. The cytotocity of AZT could be reduced with these 5 ' -O-carbonate prodrug series by delaying the 5 ' -O-glucuronidation of AZT, which is one of the major limitations of AZT.

  DOI：

  10.1021/jm010863i
• 作为产物：
  描述：

  (E)-4-(t-butyldiphenylsilyl)oxy-2-butenal 在 二异丁基氢化铝 作用下， 以 乙醚 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.42h， 生成 [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl [(E)-4-[tert-butyl(diphenyl)silyl]oxybut-2-enyl] carbonate
  参考文献：
  名称：

  New 3‘-Azido-3‘-deoxythymidin-5‘-yl O-(4-Hydroxyalkyl or -Alkenyl or -Alkylepoxide) Carbonate Prodrugs:  Synthesis and Anti-HIV Evaluation

  摘要：

  New 5 ' -O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5 ' -O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement was confirmed by comparison of the serum half-lives of the 3 ' -azido-3 ' -deoxythymidin-5 ' -yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs with our thermodynamic predictions. Interestingly, these 5 ' -O-carbonate prodrug series show increased anti-HIV potencies in conjunction with, or without, reduced cytotoxicity as compared to AZT that lead to a gain in selectivity indexes. The cytotocity of AZT could be reduced with these 5 ' -O-carbonate prodrug series by delaying the 5 ' -O-glucuronidation of AZT, which is one of the major limitations of AZT.

  DOI：

  10.1021/jm010863i

文献信息

• New 3‘-Azido-3‘-deoxythymidin-5‘-yl <i>O</i>-(4-Hydroxyalkyl or -Alkenyl or -Alkylepoxide) Carbonate Prodrugs:  Synthesis and Anti-HIV Evaluation
  作者：Patrick Vlieghe、Thierry Clerc、Christophe Pannecouque、Myriam Witvrouw、Erik De Clercq、Jean-Pierre Salles、Jean-Louis Kraus

  DOI：10.1021/jm010863i

  日期：2001.8.1

  New 5 ' -O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5 ' -O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement was confirmed by comparison of the serum half-lives of the 3 ' -azido-3 ' -deoxythymidin-5 ' -yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs with our thermodynamic predictions. Interestingly, these 5 ' -O-carbonate prodrug series show increased anti-HIV potencies in conjunction with, or without, reduced cytotoxicity as compared to AZT that lead to a gain in selectivity indexes. The cytotocity of AZT could be reduced with these 5 ' -O-carbonate prodrug series by delaying the 5 ' -O-glucuronidation of AZT, which is one of the major limitations of AZT.