5',4N-bis<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine

• 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: 5',4N-bis<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine
• 英文别名: 5',4N-bis[(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl]-2',3'-dideoxycytidine；[(2S,5R)-5-[4-[(1-methyl-4H-pyridine-3-carbonyl)amino]-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl 1-methyl-4H-pyridine-3-carboxylate
• 化学式: C₂₃H₂₇N₅O₅
• 分子量: 453.498
• InChiKey: MICHLJWXTWDTGH-AZUAARDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5',4N-bis<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine 在 氢氧化钾 作用下， 以46%的产率得到5'-<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine
  参考文献：
  名称：

  Synthesis and pharmacokinetics of a dihydropyridine chemical delivery system for the antiimmunodeficiency virus agent, dideoxycytidine

  摘要：

  In order to explore the possibility that a dihydropyridine/pyridinium redox chemical delivery system might enhance significantly the brain uptake of the anti-HIV agent dideoxycytidine (DDC), we prepared a DDC derivative which bore the 1,4-dihydro-1-methyl-3-pyridylcarbonyl moiety at both the cytidine exocyclic amino moiety and the sugar 5'-hydroxyl function; namely, [(1,4N-bis-[(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl]-2',3'-dideoxycytidine(2). In cell-free extracts of rat brain tissue, compound 2 was readily converted to free DDC by stepwise oxidation and hydrolysis of the dihydropyridyl groups. Time-dependent plasma and brain concentrations of DDC and 2 were determined following iv administration of 2 (49.3 mg/kg) to rats. Compound 2 could be detected in brain, reaching peak concentrations of 7.7 +/- 2.9 nmol/g at 15 min. Low levels of DDC also were detected with a peak concentration of 1.4 +/- 0.5 nmol/g at 240 min after injection. The brain/plasma concentration integral of compound 2 was 0.95 whereas that for DDC in brain as a ratio of combined DDC and compound 2 levels in plasma was 0.24. Despite this, brain concentrations remained low and not significantly different from those achieved following administration of DDC alone.

  DOI：

  10.1021/jm00057a002
• 作为产物：
  描述：

  2,3-二脱氧胞啶 在 吡啶 、 sodium dithionite 、 碳酸氢钠 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 反应 72.33h， 生成 5',4N-bis<(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl>-2',3'-dideoxycytidine
  参考文献：
  名称：

  Synthesis and pharmacokinetics of a dihydropyridine chemical delivery system for the antiimmunodeficiency virus agent, dideoxycytidine

  摘要：

  In order to explore the possibility that a dihydropyridine/pyridinium redox chemical delivery system might enhance significantly the brain uptake of the anti-HIV agent dideoxycytidine (DDC), we prepared a DDC derivative which bore the 1,4-dihydro-1-methyl-3-pyridylcarbonyl moiety at both the cytidine exocyclic amino moiety and the sugar 5'-hydroxyl function; namely, [(1,4N-bis-[(1,4-dihydro-1-methyl-3-pyridinyl)carbonyl]-2',3'-dideoxycytidine(2). In cell-free extracts of rat brain tissue, compound 2 was readily converted to free DDC by stepwise oxidation and hydrolysis of the dihydropyridyl groups. Time-dependent plasma and brain concentrations of DDC and 2 were determined following iv administration of 2 (49.3 mg/kg) to rats. Compound 2 could be detected in brain, reaching peak concentrations of 7.7 +/- 2.9 nmol/g at 15 min. Low levels of DDC also were detected with a peak concentration of 1.4 +/- 0.5 nmol/g at 240 min after injection. The brain/plasma concentration integral of compound 2 was 0.95 whereas that for DDC in brain as a ratio of combined DDC and compound 2 levels in plasma was 0.24. Despite this, brain concentrations remained low and not significantly different from those achieved following administration of DDC alone.

  DOI：

  10.1021/jm00057a002