tert-butyl (R)-2-((S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)propanethioamido)-3-methylbutanoate | 1272391-91-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: tert-butyl (R)-2-((S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)propanethioamido)-3-methylbutanoate
• 英文别名: Fmoc-thionoAla-Val-OtBu；tert-butyl (2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoate
• CAS: 1272391-91-9
• 化学式: C₂₇H₃₄N₂O₄S
• 分子量: 482.644
• InChiKey: ZKTSCELXKMJDGF-SBUREZEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-2-((S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)propanethioamido)-3-methylbutanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (2S)-2-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanethioyl]amino]-3-methylbutanoic acid
  参考文献：
  名称：

  Cell-Permeable and Plasma-Stable Peptidomimetic Inhibitors of the Postsynaptic Density-95/N-Methyl-d-Aspartate Receptor Interaction

  摘要：

  The protein protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be :replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETA(s)V (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.

  DOI：

  10.1021/jm1013924
• 作为产物：
  描述：

  L-缬氨酸叔丁酯盐酸盐 在 劳森试剂 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 50.0h， 生成 tert-butyl (R)-2-((S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)propanethioamido)-3-methylbutanoate
  参考文献：
  名称：

  Cell-Permeable and Plasma-Stable Peptidomimetic Inhibitors of the Postsynaptic Density-95/N-Methyl-d-Aspartate Receptor Interaction

  摘要：

  The protein protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be :replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETA(s)V (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.

  DOI：

  10.1021/jm1013924

文献信息

• Cell-Permeable and Plasma-Stable Peptidomimetic Inhibitors of the Postsynaptic Density-95/<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Interaction
  作者：Anders Bach、Jonas N. N. Eildal、Nicolai Stuhr-Hansen、Rasmus Deeskamp、Marie Gottschalk、Søren W. Pedersen、Anders S. Kristensen、Kristian Strømgaard

  DOI：10.1021/jm1013924

  日期：2011.3.10

  The protein protein interaction between the NMDA receptor and its intracellular scaffolding protein, PSD-95, is a potential target for treating ischemic brain diseases, neuropathic pain, and Alzheimer's disease. We have previously demonstrated that N-alkylated tetrapeptides are potent inhibitors of this interaction, and here, this template is exploited for the development of blood plasma-stable and cell-permeable inhibitors. Initially, we explored both the amino acid sequence of the tetrapeptide and the nature of the N-alkyl groups, which consolidated N-cyclohexylethyl-ETAV (1) as the most potent and selective compound. Next, the amide moieties of N-methylated ETAV were systematically replaced with thioamides, demonstrating that one of three amide bonds could be :replaced without compromising the affinity. Subsequent optimization of the N-alkyl groups and evaluation of cell permeability led to identification of N-cyclohexylethyl-ETA(s)V (54) as the most potent, plasma-stable and cell-permeable inhibitor, which is a promising tool in unraveling the therapeutic potential of the PSD-95/NMDA receptor interaction.