| 1447805-49-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• CAS: 1447805-49-3
• 化学式: C₁₀H₁₄N₂O₂S
• 分子量: 226.299
• InChiKey: HFDTUTNBNVPYAR-LJJSCBMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.51
• 重原子数：
  15.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  73.05
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  、 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-2-[[(2S)-2-azido-3-phenylpropanoyl]amino]-4-methyl-N-[(2S)-4-methyl-1-[[(E,2S)-4-methylsulfonyl-1-pyridin-4-ylbut-3-en-2-yl]amino]-1-oxopentan-2-yl]pentanamide
  参考文献：
  名称：

  Incorporation of Non-natural Amino Acids Improves Cell Permeability and Potency of Specific Inhibitors of Proteasome Trypsin-like Sites

  摘要：

  Proteasomes degrade the majority of proteins in mammalian cells by a concerted action of three distinct pairs of active sites. The chymotrypsin-like sites are targets of antimyeloma agents bortezomib and carfilzomib. Inhibitors of the trypsin-like site sensitize multiple myeloma cells to these agents. Here we describe systematic effort to develop inhibitors with improved potency and cell permeability, yielding azido-Phe-Leu-Leu-4-aminomethyl-Phe-methyl vinyl sulfone (4a, LU-102), and a fluorescent activity-based probe for this site. X-ray structures of 4a and related inhibitors complexed with yeast proteasomes revealed the structural basis for specificity. Nontoxic to myeloma cells when used as a single agent, 4a sensitized them to bortezomib and carfilzomib. This sensitizing effect was much stronger than the synergistic effects of histone acetylase inhibitors or additive effects of doxorubicin and dexamethasone, raising the possibility that cornbinations of inhibitors of the trypsin-like site with bortezomib or carfilzomib would have stronger antincoplastic activity than combinations currently used clinically.

  DOI：

  10.1021/jm3016987