N-{1-[(2R,3S,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-2-[2-(tert-butyl-dimethyl-silanyloxy)-acetylamino]-2-methyl-propionamide | 184002-69-5

• 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: N-{1-[(2R,3S,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-2-[2-(tert-butyl-dimethyl-silanyloxy)-acetylamino]-2-methyl-propionamide
• CAS: 184002-69-5
• 化学式: C₃₉H₇₈N₄O₈Si₄
• 分子量: 843.412
• InChiKey: VFAHDYNSCFPIEO-ZHKQUFGTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  55.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  139.24
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-{1-[(2R,3S,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-2-[2-(tert-butyl-dimethyl-silanyloxy)-acetylamino]-2-methyl-propionamide 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以65%的产率得到N-[1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]-2-[(2-hydroxyacetyl)amino]-2-methylpropanamide
  参考文献：
  名称：

  Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

  摘要：

  N-4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of am-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N-4 prevented nonspecific proteolytic cleavage in biological medium. Aln-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N-4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N-4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00153-8
• 作为产物：
  描述：

  阿糖胞苷 在 咪唑 、 4-二甲氨基吡啶 、 正丁基锂 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 N-{1-[(2R,3S,4R,5R)-3,4-Bis-(tert-butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-tetrahydro-furan-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-2-[2-(tert-butyl-dimethyl-silanyloxy)-acetylamino]-2-methyl-propionamide
  参考文献：
  名称：

  Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity

  摘要：

  N-4-Dipeptidyl slow-release forms of the anticancer drug ara-C were prepared by acylation of the lithiated nucleotide with 4,4-dialkyloxazolinones. An azapeptide prodrug of am-C was obtained by condensation of an amino acid hydrazide with an activated nucleotide urea. The use of unnatural amino acid residues at N-4 prevented nonspecific proteolytic cleavage in biological medium. Aln-C prodrugs 10, 15, 17, and 19 released active drug with half-lives from a few minutes to several days, respectively. Activation via intramolecular N-4-deacylation did not require enzymatic intervention but was strictly dependent on the structure of the peptide chain. The prodrugs 10, 15, and 17 produced similar growth inhibition as ara-C in cultured murine leukemia cells while the azapeptide prodrug 19 was less potent reflecting the slow release of active drug with this compound. All four prodrugs retained the ability to induce apoptosis in human HL-60 leukemia cells with kinetics dictated by the rate of intramolecular N-4-deacylation. This the first demonstration for the control of apoptotic cell death by the modulation of drug release from prodrugs. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00153-8