[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-12-[5-(dimethylamino)-5-oxopentanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 1093959-23-9

• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-12-[5-(dimethylamino)-5-oxopentanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 1093959-23-9
• 化学式: C₅₂H₆₀N₂O₁₅
• 分子量: 953.053
• InChiKey: UOTOASQIDLSZNP-YSLASLGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  69
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  242
• 氢给体数：
  4
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  在 吡啶 、 氢氟酸 作用下， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-12-[5-(dimethylamino)-5-oxopentanoyl]oxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Paclitaxel succinate analogs: Anionic and amide introduction as a strategy to impart blood–brain barrier permeability

  摘要：

  A focused library of TX-67 (C10 hemi-succinate) analogs has been prepared, including C7 regioisomers, esters, amides, and one-carbon homologs. These were prepared to investigate whether the lack of TX-67 interaction with P-glycoprotein (Pgp) is due to the presence of the carboxylic acid moiety and whether this phenomenon was restricted to C10 analogs. Tubulin stabilization ability, cytotoxicity, and Pgp interactions were evaluated. All carboxylic acid analogs and several of the amides had no apparent interactions with Pgp at the concentrations used, whereas the ester variants displayed characteristics of Pgp substrates. Furthermore, it was demonstrated that hydrogen-bonding properties were significant with respect to Pgp interactions. Calculations of logD and cross-sectional areas revealed that these analogs are predicted to partition into the membrane and can compete for Pgp binding sites. The anionic and amide introduction strategy may allow for delivery of paclitaxel into the CNS and may be a potential approach for the delivery of other, structurally complex and lipophilic non-CNS permeable drugs. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.103