N-({[tert-Butyl(dimethyl)silyl]oxy}acetyl)-2-methylalanine | 145213-64-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-({[tert-Butyl(dimethyl)silyl]oxy}acetyl)-2-methylalanine
• 英文别名: 2-[[2-[tert-butyl(dimethyl)silyl]oxyacetyl]amino]-2-methylpropanoic acid
• CAS: 145213-64-5
• 化学式: C₁₂H₂₅NO₄Si
• 分子量: 275.42
• InChiKey: DSPUKTOUIQEWCL-UHFFFAOYSA-N

物化性质

• 沸点：
  383.8±27.0 °C(Predicted)
• 密度：
  1.022±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-({[tert-Butyl(dimethyl)silyl]oxy}acetyl)-2-methylalanine 在 4-二甲氨基吡啶 、 正丁基锂 、 N,N'-二环己基碳二亚胺 作用下， 以 乙腈 为溶剂， 反应 16.0h， 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

文献信息

• Synthesis of chemoreversible prodrugs of ara-C with variable time-release profiles. Biological evaluation of their apoptotic activity
  作者：Peter Wipf、Wenjie Li、Christianah M. Adeyeye、James M. Rusnak、John S. Lazo

  DOI：10.1016/0968-0896(96)00153-8

  日期：1996.10

  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