O-[bis(benzyloxy)phosphoryl]-N-butyryl-N'-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-L-tyrosinamide | 1268157-57-8

• 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: O-[bis(benzyloxy)phosphoryl]-N-butyryl-N'-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-L-tyrosinamide
• 英文别名: O-[bis(benzyloxy)phosphoryl]-N-butyryl-N-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-L-tyrosinamide；dibenzyl [4-[(2S)-2-(butanoylamino)-3-oxo-3-[3-(2-oxo-1,3-diazinan-1-yl)propylamino]propyl]phenyl] phosphate
• CAS: 1268157-57-8
• 化学式: C₃₄H₄₃N₄O₇P
• 分子量: 650.712
• InChiKey: NURIFPWINRJRMW-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  46
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  O-[bis(benzyloxy)phosphoryl]-N-butyryl-N'-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-L-tyrosinamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 以90%的产率得到N-butyryl-N'-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-O-phosphono-L-tyrosinamide
  参考文献：
  名称：

  Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy

  摘要：

  We report a novel series of non-peptide ligands that inhibit the growth factor receptor-bound protein 2 (Grb2)-Src homology 2 (SH2) domain binding, designed using a combined computational and NMR-driven approach. We have identified a new lead compound, in (IC50 = 56 mu M), which is cytotoxic in HER2-positive breast cancer cells and disrupts the interaction between HER2 and Grb2. Thus, In can be used as a scaffold for the development of efficient Grb2-SH2 domain binding inhibitors.

  DOI：

  10.1021/jm101478n
• 作为产物：
  描述：

  C₁₉H₃₁NO₄Si 在 四氮唑 、 叔丁基过氧化氢 、 水 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 6.84h， 生成 O-[bis(benzyloxy)phosphoryl]-N-butyryl-N'-[3-(2-oxotetrahydropyrimidin-1(2H)-yl)propyl]-L-tyrosinamide
  参考文献：
  名称：

  Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy

  摘要：

  We report a novel series of non-peptide ligands that inhibit the growth factor receptor-bound protein 2 (Grb2)-Src homology 2 (SH2) domain binding, designed using a combined computational and NMR-driven approach. We have identified a new lead compound, in (IC50 = 56 mu M), which is cytotoxic in HER2-positive breast cancer cells and disrupts the interaction between HER2 and Grb2. Thus, In can be used as a scaffold for the development of efficient Grb2-SH2 domain binding inhibitors.

  DOI：

  10.1021/jm101478n

文献信息

• Development of Non-Peptide Ligands of Growth Factor Receptor-Bound Protein 2-Src Homology 2 Domain Using Molecular Modeling and NMR Spectroscopy
  作者：Ángel L. Orcajo-Rincón、Silvia Ortega-Gutiérrez、Pedro Serrano、Ivan R. Torrecillas、Kurt Wüthrich、Mercedes Campillo、Leonardo Pardo、Alma Viso、Bellinda Benhamú、María L. López-Rodríguez

  DOI：10.1021/jm101478n

  日期：2011.2.24

  We report a novel series of non-peptide ligands that inhibit the growth factor receptor-bound protein 2 (Grb2)-Src homology 2 (SH2) domain binding, designed using a combined computational and NMR-driven approach. We have identified a new lead compound, in (IC50 = 56 mu M), which is cytotoxic in HER2-positive breast cancer cells and disrupts the interaction between HER2 and Grb2. Thus, In can be used as a scaffold for the development of efficient Grb2-SH2 domain binding inhibitors.