Tert-butyl 4-[4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-6-[4-(3-piperidin-4-ylpropyl)piperidin-1-yl]-1,3,5-triazin-2-yl]piperazine-1-carboxylate | 1447918-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Tert-butyl 4-[4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-6-[4-(3-piperidin-4-ylpropyl)piperidin-1-yl]-1,3,5-triazin-2-yl]piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-6-[4-(3-piperidin-4-ylpropyl)piperidin-1-yl]-1,3,5-triazin-2-yl]piperazine-1-carboxylate
• CAS: 1447918-97-9
• 化学式: C₃₄H₅₉N₉O₄
• 分子量: 657.9
• InChiKey: SPECXCVSKHOIOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  三聚氯氰 、 Tert-butyl 4-[4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-6-[4-(3-piperidin-4-ylpropyl)piperidin-1-yl]-1,3,5-triazin-2-yl]piperazine-1-carboxylate 以 二氯甲烷 为溶剂， 反应 12.0h， 以92%的产率得到tetra-tert-butyl 4,4',4'',4'''-(((((6-chloro-1,3,5-triazine-2,4-diyl)bis(piperidine-1,4-diyl))bis(propane-3,1-diyl))bis(piperidine-4,1-diyl))bis(1,3,5-triazine-6,2,4-triyl))tetrakis(piperazine-1-carboxylate)
  参考文献：
  名称：

  Influence of linker groups on the solubility of triazine dendrimers

  摘要：

  选择连接二胺对三嗪树状分子的溶解度有深远的影响。

  DOI：

  10.1039/c4nj00917g
• 作为产物：
  描述：

  1,3-二(4-哌啶基)丙烷 、 di(4-Boc-piperazyl)monochlorotriazine 以 甲醇 、 二氯甲烷 为溶剂， 以85%的产率得到Tert-butyl 4-[4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]-6-[4-(3-piperidin-4-ylpropyl)piperidin-1-yl]-1,3,5-triazin-2-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  Dendrimers Terminated with Dichlorotriazine Groups Provide a Route to Compositional Diversity

  摘要：

  Triazine dendrimers terminated with either four or eight dichlorotriazines can be prepared in high yields by reacting an amine-terminated dendrimer with cyanuric chloride. These materials exist as white powders and are stable to storage at room temperature. Sequential nucleophilic aromatic substitution with two different amine nucleophiles yields compounds that display the desired compositional diversity. Reaction conditions for the substitution were developed using a model dichlorotriazine with amine nucleophiles at -20,0, and 25 degrees C. Selective substitution is favored at lower temperatures and with more nucleophilic amine groups.

  DOI：

  10.1021/ol400811h

文献信息

• Design, Synthesis and Biological Assessment of a Triazine Dendrimer with Approximately 16 Paclitaxel Groups and 8 PEG Groups
  作者：Changsuk Lee、Su-Tang Lo、Jongdoo Lim、Viviana C. P. da Costa、Saleh Ramezani、Orhan K. Öz、Giovanni M. Pavan、Onofrio Annunziata、Xiankai Sun、Eric E. Simanek

  DOI：10.1021/mp400290u

  日期：2013.12.2

  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.
• Dendrimers Terminated with Dichlorotriazine Groups Provide a Route to Compositional Diversity
  作者：Subrata Patra、Brittany Kozura、Adela Y.-T. Huang、Alan E. Enciso、Xiankai Sun、Jer-Tsong Hsieh、Chai-Lin Kao、Hui-Ting Chen、Eric E. Simanek

  DOI：10.1021/ol400811h

  日期：2013.8.2

  Triazine dendrimers terminated with either four or eight dichlorotriazines can be prepared in high yields by reacting an amine-terminated dendrimer with cyanuric chloride. These materials exist as white powders and are stable to storage at room temperature. Sequential nucleophilic aromatic substitution with two different amine nucleophiles yields compounds that display the desired compositional diversity. Reaction conditions for the substitution were developed using a model dichlorotriazine with amine nucleophiles at -20,0, and 25 degrees C. Selective substitution is favored at lower temperatures and with more nucleophilic amine groups.
• Influence of linker groups on the solubility of triazine dendrimers
  作者：Alan E. Enciso、Matteo Garzoni、Giovanni M. Pavan、Eric E. Simanek

  DOI：10.1039/c4nj00917g

  日期：——

  The choice of linking diamine has profound influence on the solubility of triazine dendrimers.

  选择连接二胺对三嗪树状分子的溶解度有深远的影响。