N-(N-(9-fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-seryl)-5-aminolaevulinic acid methyl ester | 1166835-51-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(N-(9-fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-seryl)-5-aminolaevulinic acid methyl ester
• 英文别名: methyl 5-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoyl]amino]-4-oxopentanoate
• CAS: 1166835-51-3
• 化学式: C₂₈H₃₄N₂O₇
• 分子量: 510.587
• InChiKey: NKYIEFSPVDPYOH-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基酮戊酸甲酯盐酸盐 、 Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到N-(N-(9-fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-seryl)-5-aminolaevulinic acid methyl ester
  参考文献：
  名称：

  Improved Peptide Prodrugs of 5-ALA for PDT: Rationalization of Cellular Accumulation and Protoporphyrin IX Production by Direct Determination of Cellular Prodrug Uptake and Prodrug Metabolization

  摘要：

  Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an (x-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at,I concentration of 0.1 MM, L-Phe derivatives 4m and 4o, and L-Leu, L-Met, and L-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.

  DOI：

  10.1021/jm900224r

文献信息

• Improved Peptide Prodrugs of 5-ALA for PDT: Rationalization of Cellular Accumulation and Protoporphyrin IX Production by Direct Determination of Cellular Prodrug Uptake and Prodrug Metabolization
  作者：Francesca Giuntini、Ludovic Bourré、Alexander J. MacRobert、Michael Wilson、Ian M. Eggleston

  DOI：10.1021/jm900224r

  日期：2009.7.9

  Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an (x-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at,I concentration of 0.1 MM, L-Phe derivatives 4m and 4o, and L-Leu, L-Met, and L-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.