(S)-2-Amino-succinic acid 4-[2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl] ester | 355117-36-1

• 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: (S)-2-Amino-succinic acid 4-[2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl] ester
• 英文别名: (2S)-2-amino-4-[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethoxy]-4-oxobutanoic acid
• CAS: 355117-36-1
• 化学式: C₁₂H₁₆N₆O₆
• 分子量: 340.296
• InChiKey: JOLMDKKGSUMDFE-LURJTMIESA-N

物化性质

• 沸点：
  740.3±70.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  184
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (S)-2-Amino-succinic acid 4-[2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl] ester 以 phosphate buffer 为溶剂， 生成 阿昔洛韦
  参考文献：
  名称：

  Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir

  摘要：

  The objective of this work was to improve nasal absorption of relatively impermeable small drug molecules via an amino acid prodrug approach. Acyclovir was selected as a model drug. L-Aspartate beta -ester, L-lysyl, and L-phenylalanyl esters of acyclovir were synthesized to investigate their effectiveness in enhancing nasal absorption of acyclovir. A stability study was conducted in phosphate buffer under various pH conditions at 25 and 37 degreesC. Enzymatic hydrolysis in rat nasal washings and plasma was conducted at 37 degreesC. A rat in situ nasal perfusion technique was utilized in this investigation to examine the rate and extent of nasal absorption of amino acid prodrugs. The remaining analyte concentrations in the nasal perfusate were quantitated by reversed-phase high-performance liquid chromatography. The results revealed that the L-lysyl and L-phenylalanyl esters were less stable than L-aspartate beta -ester. The stability of all three esters decreased with increasing FH and temperature. L-phenylalanyl ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33 min. The rat in situ nasal perfusion study revealed that the extent of nasal absorption of acyclovir, L-lysyl and L-phenylalanyl esters was not significant (p < 1%). L-Aspartate beta -ester was absorbed to the extent of similar to8% over 90 min of perfusion at an initial drug concentration of 100 muM. Nasal absorption of L-aspartate beta -ester of acyclovir was inhibited by L-asparagine but not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir nasal absorption from the L-aspartate p-ester prodrug suggests that nasal uptake of this prodrug probably involves an active transport system. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:617-624, 2001.

  DOI：

  10.1002/1520-6017(200105)90:5<617::aid-jps1018>3.0.co;2-5
• 作为产物：
  描述：

  阿昔洛韦 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 (S)-2-Amino-succinic acid 4-[2-(2-amino-6-oxo-1,6-dihydro-purin-9-ylmethoxy)-ethyl] ester
  参考文献：
  名称：

  Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir

  摘要：

  The objective of this work was to improve nasal absorption of relatively impermeable small drug molecules via an amino acid prodrug approach. Acyclovir was selected as a model drug. L-Aspartate beta -ester, L-lysyl, and L-phenylalanyl esters of acyclovir were synthesized to investigate their effectiveness in enhancing nasal absorption of acyclovir. A stability study was conducted in phosphate buffer under various pH conditions at 25 and 37 degreesC. Enzymatic hydrolysis in rat nasal washings and plasma was conducted at 37 degreesC. A rat in situ nasal perfusion technique was utilized in this investigation to examine the rate and extent of nasal absorption of amino acid prodrugs. The remaining analyte concentrations in the nasal perfusate were quantitated by reversed-phase high-performance liquid chromatography. The results revealed that the L-lysyl and L-phenylalanyl esters were less stable than L-aspartate beta -ester. The stability of all three esters decreased with increasing FH and temperature. L-phenylalanyl ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33 min. The rat in situ nasal perfusion study revealed that the extent of nasal absorption of acyclovir, L-lysyl and L-phenylalanyl esters was not significant (p < 1%). L-Aspartate beta -ester was absorbed to the extent of similar to8% over 90 min of perfusion at an initial drug concentration of 100 muM. Nasal absorption of L-aspartate beta -ester of acyclovir was inhibited by L-asparagine but not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir nasal absorption from the L-aspartate p-ester prodrug suggests that nasal uptake of this prodrug probably involves an active transport system. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:617-624, 2001.

  DOI：

  10.1002/1520-6017(200105)90:5<617::aid-jps1018>3.0.co;2-5

文献信息

• Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir
  作者：Chun Yang、Hongwu Gao、Ashim K. Mitra

  DOI：10.1002/1520-6017(200105)90:5<617::aid-jps1018>3.0.co;2-5

  日期：2001.5

  The objective of this work was to improve nasal absorption of relatively impermeable small drug molecules via an amino acid prodrug approach. Acyclovir was selected as a model drug. L-Aspartate beta -ester, L-lysyl, and L-phenylalanyl esters of acyclovir were synthesized to investigate their effectiveness in enhancing nasal absorption of acyclovir. A stability study was conducted in phosphate buffer under various pH conditions at 25 and 37 degreesC. Enzymatic hydrolysis in rat nasal washings and plasma was conducted at 37 degreesC. A rat in situ nasal perfusion technique was utilized in this investigation to examine the rate and extent of nasal absorption of amino acid prodrugs. The remaining analyte concentrations in the nasal perfusate were quantitated by reversed-phase high-performance liquid chromatography. The results revealed that the L-lysyl and L-phenylalanyl esters were less stable than L-aspartate beta -ester. The stability of all three esters decreased with increasing FH and temperature. L-phenylalanyl ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33 min. The rat in situ nasal perfusion study revealed that the extent of nasal absorption of acyclovir, L-lysyl and L-phenylalanyl esters was not significant (p < 1%). L-Aspartate beta -ester was absorbed to the extent of similar to8% over 90 min of perfusion at an initial drug concentration of 100 muM. Nasal absorption of L-aspartate beta -ester of acyclovir was inhibited by L-asparagine but not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir nasal absorption from the L-aspartate p-ester prodrug suggests that nasal uptake of this prodrug probably involves an active transport system. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:617-624, 2001.