1,3-Bis[(2,2,2-trifluoroacetyl)amino]propan-2-yl 5-oxohexanoate | 1396670-63-5

• 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: 1,3-Bis[(2,2,2-trifluoroacetyl)amino]propan-2-yl 5-oxohexanoate
• 英文别名: 1,3-bis[(2,2,2-trifluoroacetyl)amino]propan-2-yl 5-oxohexanoate
• CAS: 1396670-63-5
• 化学式: C₁₃H₁₆F₆N₂O₅
• 分子量: 394.271
• InChiKey: LVDOVLWWGJIGSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1,3-bis-(trifluoroacetamido)-isopropanol 、 5-氧代己酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1,3-Bis[(2,2,2-trifluoroacetyl)amino]propan-2-yl 5-oxohexanoate
  参考文献：
  名称：

  pH-Triggered Release of Platinum Drugs Conjugated to Micelles via an Acid-Cleavable Linker

  摘要：

  A new acid-degradable polymer platinum conjugate was prepared by postmodification of a POEGMEMA-b-PHEMA block copolymer obtained by RAFT polymerization. A hydrazone linkage, susceptible to hydrolytic cleavage, was formed by reaction of the carbonyl group of a diamino ligand with the hydrazide-modified copolymer. According to NMR kinetic studies, degradation of the hydrazone bond was observed to be more than 10 times faster at pH 5.5 than at pH 7.4. The platinum drug was introduced on the copolymer by permanent conjugation onto the diamino conjugation sites. The platinated amphiphilic copolymer was subsequently self-assembled into nanosized micelles of 27 nm with the platinum drug safely encapsulated in the core. Extended conjugation time however led to cross-linking and to particles of more than 1000 nm. In vitro experiments revealed a high cytotoxicity for the platinum drug-bearing small micelles compared to the polymer before conjugation. In contrast, the large particle did not show any toxicity since the size prevents endocytosis. However, endocytosis and the subsequent location of the micelles in the acidic endosomes or lysosomes are necessary to trigger the release of the toxic platinum drug. In contrast, the small drug loaded micelle exhibited a toxicity superior to the underlying low-molecular-weight drug (IC50 = 10.5 mu M vs 17 mu M) These hydrolytically degradable nanovectors constitute a promising system for a triggered release of platinum drugs.

  DOI：

  10.1021/ma3012812

文献信息

• pH-Triggered Release of Platinum Drugs Conjugated to Micelles via an Acid-Cleavable Linker
  作者：Sandra Binauld、Wei Scarano、Martina H. Stenzel

  DOI：10.1021/ma3012812

  日期：2012.9.11

  A new acid-degradable polymer platinum conjugate was prepared by postmodification of a POEGMEMA-b-PHEMA block copolymer obtained by RAFT polymerization. A hydrazone linkage, susceptible to hydrolytic cleavage, was formed by reaction of the carbonyl group of a diamino ligand with the hydrazide-modified copolymer. According to NMR kinetic studies, degradation of the hydrazone bond was observed to be more than 10 times faster at pH 5.5 than at pH 7.4. The platinum drug was introduced on the copolymer by permanent conjugation onto the diamino conjugation sites. The platinated amphiphilic copolymer was subsequently self-assembled into nanosized micelles of 27 nm with the platinum drug safely encapsulated in the core. Extended conjugation time however led to cross-linking and to particles of more than 1000 nm. In vitro experiments revealed a high cytotoxicity for the platinum drug-bearing small micelles compared to the polymer before conjugation. In contrast, the large particle did not show any toxicity since the size prevents endocytosis. However, endocytosis and the subsequent location of the micelles in the acidic endosomes or lysosomes are necessary to trigger the release of the toxic platinum drug. In contrast, the small drug loaded micelle exhibited a toxicity superior to the underlying low-molecular-weight drug (IC50 = 10.5 mu M vs 17 mu M) These hydrolytically degradable nanovectors constitute a promising system for a triggered release of platinum drugs.