N-(1-D,L-carboxytridecyl)-1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronamide | 669011-12-5

• 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-(1-D,L-carboxytridecyl)-1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronamide
• 英文别名: 2-[[(2S,3S,4S,5R,6S)-3,4,5,6-tetraacetyloxyoxane-2-carbonyl]amino]tetradecanoic acid
• CAS: 669011-12-5
• 化学式: C₂₈H₄₅NO₁₂
• 分子量: 587.665
• InChiKey: HXHOCMCNTQXOGT-RNDFWVNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  41.0
• 可旋转键数：
  18.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  180.83
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  N-(1-D,L-carboxytridecyl)-1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronamide 在 sodium methylate 作用下， 反应 2.0h， 以95%的产率得到N-(1-D,L-carboxytridecyl)-α,β-D-glucopyranuronamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Liposaccharide Drug Delivery Agent:  Application to the Gastrointestinal Absorption of Gentamicin

  摘要：

  The design, synthesis, and evaluation of a liposaccharide (11) for use as an agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs with poor membrane permeability is reported. 11 was designed to possess both surfactant and ion-pairing properties and was conveniently synthesized from D-glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in good yield. Isothermal titration microcalorimetry was used to determine the critical micelle concentration of 11 (in PBS) to be 2.09 +/- 0.01 mM with an enthalpy of demicellization of 4.91 +/- 0.11 kJ/mol. The ability of 11 to enhance the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1), a hydrophilic polycation with negligible oral bioavailability, was assessed in vivo using rats. Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60 mg/kg) had a statistically significant (P less than or equal to 0.034) increase in C-max, AUC(120), and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone. The highest bioavailability (F = 9.1 +/- 2.0%) was achieved by dosing with the mixture 11 (100 mg/kg) and 1 (15 mg/kg). This represents a 6-fold increase in bioavailability compared to the control (F = 1.4 +/- 0.3%). These results suggest that the molar ratio of 1:11 may be critical in optimizing the delivery system, a finding ascribed in part to the ion-pairing properties of 11. The effect of 11 on the gastrointestinal mucosa was assessed using light microscopy to examine tissue samples from rats used in the pharmacokinetic study. No morphological changes were found in either the esophagi or duodena of the rats examined. One rat dosed with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which could be attributed to 11.

  DOI：

  10.1021/jm030474j
• 作为产物：
  描述：

  N-[1-D,L-(benzyloxycarbonyl)tridecyl]-1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronamide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以99%的产率得到N-(1-D,L-carboxytridecyl)-1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Liposaccharide Drug Delivery Agent:  Application to the Gastrointestinal Absorption of Gentamicin

  摘要：

  The design, synthesis, and evaluation of a liposaccharide (11) for use as an agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs with poor membrane permeability is reported. 11 was designed to possess both surfactant and ion-pairing properties and was conveniently synthesized from D-glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in good yield. Isothermal titration microcalorimetry was used to determine the critical micelle concentration of 11 (in PBS) to be 2.09 +/- 0.01 mM with an enthalpy of demicellization of 4.91 +/- 0.11 kJ/mol. The ability of 11 to enhance the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1), a hydrophilic polycation with negligible oral bioavailability, was assessed in vivo using rats. Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60 mg/kg) had a statistically significant (P less than or equal to 0.034) increase in C-max, AUC(120), and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone. The highest bioavailability (F = 9.1 +/- 2.0%) was achieved by dosing with the mixture 11 (100 mg/kg) and 1 (15 mg/kg). This represents a 6-fold increase in bioavailability compared to the control (F = 1.4 +/- 0.3%). These results suggest that the molar ratio of 1:11 may be critical in optimizing the delivery system, a finding ascribed in part to the ion-pairing properties of 11. The effect of 11 on the gastrointestinal mucosa was assessed using light microscopy to examine tissue samples from rats used in the pharmacokinetic study. No morphological changes were found in either the esophagi or duodena of the rats examined. One rat dosed with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which could be attributed to 11.

  DOI：

  10.1021/jm030474j