L-Phenylalanine, N-acetyl-4-(difluorophosphonomethyl)- | 150618-11-4

• 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: L-Phenylalanine, N-acetyl-4-(difluorophosphonomethyl)-
• 英文别名: (S)-2-Acetylamino-3-[4-(difluoro-phosphono-methyl)-phenyl]-propionic acid
• CAS: 150618-11-4
• 化学式: C₁₂H₁₄F₂NO₆P
• 分子量: 337.217
• InChiKey: BTTXXADLPAVKRU-JTQLQIEISA-N

物化性质

• 密度：
  1.533±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.05
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123.93
• 氢给体数：
  4.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  L-Phenylalanine, N-acetyl-4-(difluorophosphonomethyl)- 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 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 为溶剂， 反应 6.0h， 生成 [1S-[1R*[R*(R*)]]]-[(4-{2-Acetylamino-2-[1-(1-dihexylcarbamoyl-ethylcarbamoyl)-2-methyl-propyl-carbamoyl]-ethyl}-phenyl)-difluoro-methyl]-phosphonic acid
  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：

  4-((S)-2-Benzyloxycarbonyl-2-tert-butoxycarbonylamino-ethyl)-benzoic acid 2-trimethylsilanyl-ethyl ester 在 palladium on activated charcoal 、 N,N-二甲基甲酰胺 N-甲基吗啉 、 盐酸 、 molecular sieve 、 草酰氯 、 三甲基溴硅烷 、 二乙胺基三氟化硫 、 茴香硫醚 、 四丁基氟化铵 、 氢气 、 间甲酚 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 、 三氟乙酸 为溶剂， 反应 53.0h， 生成 L-Phenylalanine, N-acetyl-4-(difluorophosphonomethyl)-
  参考文献：
  名称：

  制备L-（膦二氟甲基）苯丙氨酸衍生物作为O-磷酸酪氨酸的不可水解模拟物

  摘要：

  Nt-BOC-L-（膦二氟甲基）苯丙氨酸苄酯（1）由Nt-BOC-L-酪氨酸苄基酯O-三氟甲磺酸酯（4）分5步制备。将化合物1进一步转化为可能适合于肽合成的衍生物2和3。类似物1-3是O-磷酸酪氨酸的不可水解模拟物。

  DOI：

  10.1016/s0040-4039(00)73631-8