N¹-((diethylamino)ethyl-N⁴-(1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-ylamino)-4-methyl-1-oxopentan-2-yl)terephthalamide | 869805-74-3

• 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: N¹-((diethylamino)ethyl-N⁴-(1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-ylamino)-4-methyl-1-oxopentan-2-yl)terephthalamide
• 英文别名: 1-N-[2-(diethylamino)ethyl]-4-N-[(2S)-1-[[(2S)-1-[methoxy(methyl)amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzene-1,4-dicarboxamide
• CAS: 869805-74-3
• 化学式: C₃₁H₄₅N₅O₅
• 分子量: 567.729
• InChiKey: FHXLQTYWNKHGBD-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N¹-((diethylamino)ethyl-N⁴-(1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-ylamino)-4-methyl-1-oxopentan-2-yl)terephthalamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以71%的产率得到N-(2-Diethylamino-ethyl)-N'-[(S)-1-((S)-1-formyl-3-methyl-butylcarbamoyl)-2-phenyl-ethyl]-terephthalamide
  参考文献：
  名称：

  Preliminary Studies of New Proteasome Inhibitors in the Tumor Targeting Approach: Synthesis and in Vitro Cytotoxicity

  摘要：

  The proteasome is a multicatalytic protease that plays a critical role in the cell. The control of proteasomes could, thus, provide a weapon for the treatment of cancer. Therefore, we have synthesized six new peptide aldehyde inhibitors of the proteasome linked to the N-(2-diethylaminoethyl)benzamide (BZA-CO) structure, in order to target the cytotoxic activity to malignant melanoma cells. Biological studies demonstrated the influence of length and composition of the amino acid chain on the cytotoxicity of our compounds. Among them, compound 19 presents the highest cytotoxicity (IC50 = 0.64 +/- 0.07 mu mol): this cytotoxicity was maintained in the presence of BZA-CO but decreased 8-fold compared to the control MG132. Fluorescence activated cell sorter (FACS) and cytotoxic activity analysis demonstrated the selectivity of compound 19 for melanoma cells. Finally, western blottings of ubiquitinated proteins in IPC227F cells as well as proteasome assays confirmed that the cytotoxicity was linked to an inhibition of the proteasome activity.

  DOI：

  10.1021/jm050181l
• 作为产物：
  描述：

  对苯二甲酸二甲酯 在 lithium hydroxide 、 三甲基铝 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 81.0h， 生成 N¹-((diethylamino)ethyl-N⁴-(1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-ylamino)-4-methyl-1-oxopentan-2-yl)terephthalamide
  参考文献：
  名称：

  Preliminary Studies of New Proteasome Inhibitors in the Tumor Targeting Approach: Synthesis and in Vitro Cytotoxicity

  摘要：

  The proteasome is a multicatalytic protease that plays a critical role in the cell. The control of proteasomes could, thus, provide a weapon for the treatment of cancer. Therefore, we have synthesized six new peptide aldehyde inhibitors of the proteasome linked to the N-(2-diethylaminoethyl)benzamide (BZA-CO) structure, in order to target the cytotoxic activity to malignant melanoma cells. Biological studies demonstrated the influence of length and composition of the amino acid chain on the cytotoxicity of our compounds. Among them, compound 19 presents the highest cytotoxicity (IC50 = 0.64 +/- 0.07 mu mol): this cytotoxicity was maintained in the presence of BZA-CO but decreased 8-fold compared to the control MG132. Fluorescence activated cell sorter (FACS) and cytotoxic activity analysis demonstrated the selectivity of compound 19 for melanoma cells. Finally, western blottings of ubiquitinated proteins in IPC227F cells as well as proteasome assays confirmed that the cytotoxicity was linked to an inhibition of the proteasome activity.

  DOI：

  10.1021/jm050181l

文献信息

• Preliminary Studies of New Proteasome Inhibitors in the Tumor Targeting Approach: Synthesis and in Vitro Cytotoxicity
  作者：Magali Vivier、Anne-Sophie Jarrousse、Bernadette Bouchon、Marie-Josephe Galmier、Philippe Auzeloux、Jacques Sauzieres、Jean-Claude Madelmont

  DOI：10.1021/jm050181l

  日期：2005.10.1

  The proteasome is a multicatalytic protease that plays a critical role in the cell. The control of proteasomes could, thus, provide a weapon for the treatment of cancer. Therefore, we have synthesized six new peptide aldehyde inhibitors of the proteasome linked to the N-(2-diethylaminoethyl)benzamide (BZA-CO) structure, in order to target the cytotoxic activity to malignant melanoma cells. Biological studies demonstrated the influence of length and composition of the amino acid chain on the cytotoxicity of our compounds. Among them, compound 19 presents the highest cytotoxicity (IC50 = 0.64 +/- 0.07 mu mol): this cytotoxicity was maintained in the presence of BZA-CO but decreased 8-fold compared to the control MG132. Fluorescence activated cell sorter (FACS) and cytotoxic activity analysis demonstrated the selectivity of compound 19 for melanoma cells. Finally, western blottings of ubiquitinated proteins in IPC227F cells as well as proteasome assays confirmed that the cytotoxicity was linked to an inhibition of the proteasome activity.