(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-[2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]-2-oxoethoxy]-5-oxopentanoic acid | 1359158-08-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-[2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]-2-oxoethoxy]-5-oxopentanoic acid
• CAS: 1359158-08-9
• 化学式: C₃₀H₄₀N₁₀O₈
• 分子量: 668.71
• InChiKey: HLFBFGABUZHLRG-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  48
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  267
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-[2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]-2-oxoethoxy]-5-oxopentanoic acid 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 (2S)-5-[2-(3-aminopropylamino)-2-oxoethoxy]-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-oxopentanoic acid;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for cancer cell targeting

  摘要：

  Cancer-targeting drug delivery can be based on the rational design of a therapeutic platform. This approach is typically achieved by the functionalization of a nanoparticle with two distinct types of molecules, a targeting ligand specific for a cancer cell, and a cytotoxic molecule to kill the cell. The present study aims to evaluate the validity of an alternative simplified approach in the design of cancer-targeting nanotherapeutics: conjugating a single type of molecule with dual activities to nanoparticles, instead of coupling a pair of orthogonal molecules. Herein we investigate whether this strategy can be validated by its application to methotrexate, a dual-acting small molecule that shows cytotoxicity because of its potent inhibitory activity against dihydrofolate reductase and that binds folic acid receptor, a tumor biomarker frequently upregulated on the cancer cell surface. This article describes a series of dendrimer conjugates derived from a generation 5 polyamidoamine (G5 PAMAM) presenting a multivalent array of methotrexate and also demonstrates their dual biological activities by surface plasmon resonance spectroscopy, a cell-free enzyme assay, and cell-based experiments with KB cancer cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.027
• 作为产物：
  描述：

  N-叔丁氧羰基-1,3-丙二胺 在 potassium carbonate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-[2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]-2-oxoethoxy]-5-oxopentanoic acid
  参考文献：
  名称：

  Dendrimer-based multivalent methotrexates as dual acting nanoconjugates for cancer cell targeting

  摘要：

  Cancer-targeting drug delivery can be based on the rational design of a therapeutic platform. This approach is typically achieved by the functionalization of a nanoparticle with two distinct types of molecules, a targeting ligand specific for a cancer cell, and a cytotoxic molecule to kill the cell. The present study aims to evaluate the validity of an alternative simplified approach in the design of cancer-targeting nanotherapeutics: conjugating a single type of molecule with dual activities to nanoparticles, instead of coupling a pair of orthogonal molecules. Herein we investigate whether this strategy can be validated by its application to methotrexate, a dual-acting small molecule that shows cytotoxicity because of its potent inhibitory activity against dihydrofolate reductase and that binds folic acid receptor, a tumor biomarker frequently upregulated on the cancer cell surface. This article describes a series of dendrimer conjugates derived from a generation 5 polyamidoamine (G5 PAMAM) presenting a multivalent array of methotrexate and also demonstrates their dual biological activities by surface plasmon resonance spectroscopy, a cell-free enzyme assay, and cell-based experiments with KB cancer cells. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.11.027