N-(3,4-dichlorophenyl)ethyl-ETA(S)V | 1272392-33-2

• 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: N-(3,4-dichlorophenyl)ethyl-ETA(S)V
• 英文别名: (4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-sulfanylidenepropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[2-(3,4-dichlorophenyl)ethylamino]-5-oxopentanoic acid
• CAS: 1272392-33-2
• 化学式: C₂₅H₃₆Cl₂N₄O₇S
• 分子量: 607.555
• InChiKey: MQVRLOSWHOLIPR-QAJIRISXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  39
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  209
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (4S)-5-[[(2S,3R)-1-[[(2S)-1-[[(1S)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-oxo-4-(4-pyren-1-ylbutylamino)pentanoic acid 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 2.0h， 以12 mg的产率得到N-(3,4-dichlorophenyl)ethyl-ETA(S)V
  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