| 1491260-69-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子
• CAS: 1491260-69-5
• 化学式: C₁₂₄H₁₄₄Cl₂N₁₄O₃₂S₄
• 分子量: 2541.75
• InChiKey: KYTKDOQUIYDJEY-WZZJJCQASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.45
• 重原子数：
  176.0
• 可旋转键数：
  50.0
• 环数：
  17.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  629.59
• 氢给体数：
  11.0
• 氢受体数：
  46.0

反应信息

• 作为产物：
  描述：

  三聚氯氰 、 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以85%的产率得到
  参考文献：
  名称：

  Design, Synthesis and Biological Assessment of a Triazine Dendrimer with Approximately 16 Paclitaxel Groups and 8 PEG Groups

  摘要：

  The synthesis and characterization of a generation three triazine dendrimer that displays a phenolic group at the core for labeling, up to eight 5 kDa PEG chains for solubility, and 16 paclitaxel groups is described. Three different diamine linkers-dipiperidine trismethylene, piperazine, and aminomethylpiperidine-were used within the dendrimer. To generate the desired stoichiometric ratio of 8 PEG chains to 16 paclitaxel groups, a monochlorotriazine was prepared with two paclitaxel groups attached through their 2'-hydroxyls using a linker containing a labile disulfide. This monochlorotriazine was linked to a dichlorotriazine with aminomethylpiperidine. The resulting dichlorotriazine bearing two paclitaxel groups could be reacted with the eight amines of the dendrimer. NMR and MALDI-TOF confirm successful reaction. The eight monochlorotriazines of the resulting material are used as the site for PEGylation affording the desired 2:1 stoichiometry. The target and intermediates were amenable to characterization by H-1 and C-13 NMR, and mass spectrometry. Analysis revealed that 16 paclitaxel groups were installed along with 5-8 PEG chains. The final construct is 63% PEG, 22% paclitaxel, and 15% triazine dendrimer. Consistent with previous efforts and computational models, 5 kDa PEG groups were essential for making the target water-soluble. Molecular dynamics simulations showed a high degree of hydration of the core, and a radius of gyration of 2.8 +/- 0.2 nm. The hydrodynamic radius of the target was found to be 15.8 nm by dynamic light scattering, an observation indicative of aggregation. Drug release studies performed in plasma showed slow and identical release in mouse and rat plasma (8%, respectively). SPECT/CT imaging was used to follow biodistribution and tumor uptake. Using a two component model, the elimination and distribution half-lives were 2.65 h and 38.2 h, respectively. Compared with previous constructs, this dendrimer persists in the vasculature longer (17.33 +/- 0.88% ID/g at 48 h postinjection), and showed higher tumor uptake. Low levels of dendrimer were observed in lung, liver, and spleen (similar to 6% ID/g). Tumor saturation studies of small prostate cancer tumors (PC3) suggest that saturation occurs at a dose between 23.2 mg/kg and 70.9 mg/kg.

  DOI：

  10.1021/mp400290u