docosan-1-yl diglycolate | 1031781-37-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: docosan-1-yl diglycolate
• 英文别名: 2-(2-Docosoxy-2-oxoethoxy)acetic acid；2-(2-docosoxy-2-oxoethoxy)acetic acid
• CAS: 1031781-37-9
• 化学式: C₂₆H₅₀O₅
• 分子量: 442.68
• InChiKey: CQEUHFXTSHEHJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  31
• 可旋转键数：
  26
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  docosan-1-yl diglycolate 、 紫杉醇 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 氯仿 为溶剂， 生成 2'-O-(5''-O-docosan-1-yldiglycoloyl)paclitaxel
  参考文献：
  名称：

  Modulating the Therapeutic Activity of Nanoparticle Delivered Paclitaxel by Manipulating the Hydrophobicity of Prodrug Conjugates

  摘要：

  A series of paclitaxel prodrugs designed for formulation in lipophilic nanoparticles are described. The hydrophobicity of paclitaxel was increased by conjugating a succession of increasingly hydrophobic lipid anchors to the drug using succinate or diglycolate cross-linkers. The prodrugs were formulated in well defined block copolymer-stabilized nanoparticles. These nanoparticles were shown to have an elimination half-life of approximately 24 h in vivo. The rate at which the prodrug was released from the nanoparticles could be controlled by adjusting the hydrophobicity of the lipid anchor, resulting in release half-lives ranging from 1 to 24 h. The diglycolate and succinate cross-linked prodrugs were 1-2 orders of magnitude less potent than paclitaxel in vitro. Nanoparticle formulations of the succinate prodrugs showed no evidence of efficacy in HT29 human colorectal tumor xenograph models. Efficacy of diglycolate prodrug nanoparticles increased as the anchor hydrophobicity increased. Long circulating diglycolate prodrug nanoparticles provided significantly enhanced therapeutic activity over commercially formulated paclitaxel at the maximum tolerated dose.

  DOI：

  10.1021/jm800002y
• 作为产物：
  描述：

  二甘醇酐 、 二十二烷-1-醇 以 吡啶 为溶剂， 生成 docosan-1-yl diglycolate
  参考文献：
  名称：

  Modulating the Therapeutic Activity of Nanoparticle Delivered Paclitaxel by Manipulating the Hydrophobicity of Prodrug Conjugates

  摘要：

  A series of paclitaxel prodrugs designed for formulation in lipophilic nanoparticles are described. The hydrophobicity of paclitaxel was increased by conjugating a succession of increasingly hydrophobic lipid anchors to the drug using succinate or diglycolate cross-linkers. The prodrugs were formulated in well defined block copolymer-stabilized nanoparticles. These nanoparticles were shown to have an elimination half-life of approximately 24 h in vivo. The rate at which the prodrug was released from the nanoparticles could be controlled by adjusting the hydrophobicity of the lipid anchor, resulting in release half-lives ranging from 1 to 24 h. The diglycolate and succinate cross-linked prodrugs were 1-2 orders of magnitude less potent than paclitaxel in vitro. Nanoparticle formulations of the succinate prodrugs showed no evidence of efficacy in HT29 human colorectal tumor xenograph models. Efficacy of diglycolate prodrug nanoparticles increased as the anchor hydrophobicity increased. Long circulating diglycolate prodrug nanoparticles provided significantly enhanced therapeutic activity over commercially formulated paclitaxel at the maximum tolerated dose.

  DOI：

  10.1021/jm800002y

文献信息

• Modulating the Therapeutic Activity of Nanoparticle Delivered Paclitaxel by Manipulating the Hydrophobicity of Prodrug Conjugates
  作者：Steven M. Ansell、Sharon A. Johnstone、Paul G. Tardi、Lily Lo、Sherwin Xie、Yu Shu、Troy O. Harasym、Natashia L. Harasym、Laura Williams、David Bermudes、Barry D. Liboiron、Walid Saad、Robert K. Prud’homme、Lawrence D. Mayer

  DOI：10.1021/jm800002y

  日期：2008.6.1

  A series of paclitaxel prodrugs designed for formulation in lipophilic nanoparticles are described. The hydrophobicity of paclitaxel was increased by conjugating a succession of increasingly hydrophobic lipid anchors to the drug using succinate or diglycolate cross-linkers. The prodrugs were formulated in well defined block copolymer-stabilized nanoparticles. These nanoparticles were shown to have an elimination half-life of approximately 24 h in vivo. The rate at which the prodrug was released from the nanoparticles could be controlled by adjusting the hydrophobicity of the lipid anchor, resulting in release half-lives ranging from 1 to 24 h. The diglycolate and succinate cross-linked prodrugs were 1-2 orders of magnitude less potent than paclitaxel in vitro. Nanoparticle formulations of the succinate prodrugs showed no evidence of efficacy in HT29 human colorectal tumor xenograph models. Efficacy of diglycolate prodrug nanoparticles increased as the anchor hydrophobicity increased. Long circulating diglycolate prodrug nanoparticles provided significantly enhanced therapeutic activity over commercially formulated paclitaxel at the maximum tolerated dose.