(S)-2-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-methyl-N-((S)-1-phenethylcarbamoyl-ethyl)-butyramide | 1026823-66-4

• 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: (S)-2-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-methyl-N-((S)-1-phenethylcarbamoyl-ethyl)-butyramide
• 英文别名: Ac-Tyr-Val-Ala-NHEtPh；(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methyl-N-[(2S)-1-oxo-1-(2-phenylethylamino)propan-2-yl]butanamide
• CAS: 1026823-66-4
• 化学式: C₂₇H₃₆N₄O₅
• 分子量: 496.607
• InChiKey: BXDIRHCCAHWBDZ-NWVWQQAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  137
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-methyl-N-((S)-1-phenethylcarbamoyl-ethyl)-butyramide 在 四氮唑 、 叔丁基过氧化氢 、 N,N-二乙基亚磷酰胺二叔丁酯 、 三氟乙酸 作用下， 生成 Phosphoric acid mono-(4-{(S)-2-acetylamino-2-[(S)-2-methyl-1-((S)-1-phenethylcarbamoyl-ethylcarbamoyl)-propylcarbamoyl]-ethyl}-phenyl) ester
  参考文献：
  名称：

  Design of Peptidomimetics That Inhibit the Association of Phosphatidylinositol 3-Kinase with Platelet-Derived Growth Factor-β Receptor and Possess Cellular Activity

  摘要：

  Phosphorylated tyrosine residues of growth factor receptors that associate with intracellular proteins containing src-homology 2 (SH2) domains are integral components in several signal transduction pathways related to proliferative diseases such as cancer, atherosclerosis, and restenosis. In particular, a phosphorylated pentapeptide [pTyr(751)-Val-Pro-Met(754)-Leu (PTyr = phosphotyrosine)] derived from the primary sequence of platelet-derived growth factor-beta (PDGF-beta) receptor blocks the association of the C-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to PDGF-beta receptor with an IC50 of 0.445 +/- 0.047 mu M. Further evaluation of the structure-activity relationships for pTyr(751)-Val-Pro-Met-Leu resulted in the design of smaller peptidomimetics with enhanced affinity including Ac-pTyr-Val-Ala-N(C6H13)(2) (IC50 = 0.076 +/- 0.010 mu M). In addition, the phosphotyrosine residue was replaced with a difluorophosphonate derivative [4-phosphono(difluoromethyl)phenylalanine (CF(2)Pmp)] which has been shown to be stable to cellular phosphatases. The extracellular administration of either CF(2)Pmp-Val-Pro-Met-Leu or Ac-CF(2)Pmp-Val-Pro-Met-NH2 in a whole cell assay resulted in specific inhibition of the PDGF-stimulated association from the C-terminal SH2 domain of the p85 subunit of PI 3-kinase to the PDGF-beta receptor in a dose-dependent manner. These compounds were also effective in inhibiting GLUT4 translocation, c-fos expression, and cell membrane ruffling in single-cell microinjection assay.

  DOI：

  10.1021/jm9802766
• 作为产物：
  描述：

  (S)-2-{(S)-2-[(S)-2-Acetylamino-3-(4-benzyloxy-phenyl)-propionylamino]-3-methyl-butyrylamino}-propionic acid 在 palladium on activated charcoal N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 (S)-2-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-methyl-N-((S)-1-phenethylcarbamoyl-ethyl)-butyramide
  参考文献：
  名称：

  Design of Peptidomimetics That Inhibit the Association of Phosphatidylinositol 3-Kinase with Platelet-Derived Growth Factor-β Receptor and Possess Cellular Activity

  摘要：

  Phosphorylated tyrosine residues of growth factor receptors that associate with intracellular proteins containing src-homology 2 (SH2) domains are integral components in several signal transduction pathways related to proliferative diseases such as cancer, atherosclerosis, and restenosis. In particular, a phosphorylated pentapeptide [pTyr(751)-Val-Pro-Met(754)-Leu (PTyr = phosphotyrosine)] derived from the primary sequence of platelet-derived growth factor-beta (PDGF-beta) receptor blocks the association of the C-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to PDGF-beta receptor with an IC50 of 0.445 +/- 0.047 mu M. Further evaluation of the structure-activity relationships for pTyr(751)-Val-Pro-Met-Leu resulted in the design of smaller peptidomimetics with enhanced affinity including Ac-pTyr-Val-Ala-N(C6H13)(2) (IC50 = 0.076 +/- 0.010 mu M). In addition, the phosphotyrosine residue was replaced with a difluorophosphonate derivative [4-phosphono(difluoromethyl)phenylalanine (CF(2)Pmp)] which has been shown to be stable to cellular phosphatases. The extracellular administration of either CF(2)Pmp-Val-Pro-Met-Leu or Ac-CF(2)Pmp-Val-Pro-Met-NH2 in a whole cell assay resulted in specific inhibition of the PDGF-stimulated association from the C-terminal SH2 domain of the p85 subunit of PI 3-kinase to the PDGF-beta receptor in a dose-dependent manner. These compounds were also effective in inhibiting GLUT4 translocation, c-fos expression, and cell membrane ruffling in single-cell microinjection assay.

  DOI：

  10.1021/jm9802766