tert-butyl ((S)-1-(((S)-1-((5-bromopentyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)carbamate | 1286282-16-3

• 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: tert-butyl ((S)-1-(((S)-1-((5-bromopentyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)carbamate
• CAS: 1286282-16-3
• 化学式: C₂₅H₃₆BrN₅O₄
• 分子量: 550.496
• InChiKey: IKWDVIVQFUXTQB-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.25
• 重原子数：
  35.0
• 可旋转键数：
  13.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  125.21
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((S)-1-(((S)-1-((5-bromopentyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)carbamate 以 二氯甲烷 、 乙腈 为溶剂， 生成 (S)-2-amino-3-(1H-imidazol-4-yl)-N-((S)-1-oxo-3-phenyl-1-(5-(pyrrolidin-1-yl)pentylamino)propan-2-yl)propanamide
  参考文献：
  名称：

  Small-Molecule Ligands of Methyl-Lysine Binding Proteins

  摘要：

  Proteins which bind methylated lysines ("readers" of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a repressed transcriptional state. Antagonists of MBT domains would serve as probes to interrogate the functional role of these proteins and initiate the chemical biology of methyl-lysine readers as a target class. Small-molecule MBT antagonists were designed based on the structure of histone peptide - MBT complexes and their interaction with MBT domains determined using a chemiluminescent assay and ITC. The ligands discovered antagonize native histone peptide binding, exhibiting 5-fold stronger binding affinity to L3MBTL1 than its preferred histone peptide. The first cocrystal structure of a small molecule bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design.

  DOI：

  10.1021/jm200045v
• 作为产物：
  描述：

  tert-butyl ((S)-1-(((S)-1-((5-hydroxypentyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)carbamate 在 四溴化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到tert-butyl ((S)-1-(((S)-1-((5-bromopentyl)amino)-1-oxo-3-phenylpropan-2-yl)amino)-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  Small-Molecule Ligands of Methyl-Lysine Binding Proteins

  摘要：

  Proteins which bind methylated lysines ("readers" of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a repressed transcriptional state. Antagonists of MBT domains would serve as probes to interrogate the functional role of these proteins and initiate the chemical biology of methyl-lysine readers as a target class. Small-molecule MBT antagonists were designed based on the structure of histone peptide - MBT complexes and their interaction with MBT domains determined using a chemiluminescent assay and ITC. The ligands discovered antagonize native histone peptide binding, exhibiting 5-fold stronger binding affinity to L3MBTL1 than its preferred histone peptide. The first cocrystal structure of a small molecule bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design.

  DOI：

  10.1021/jm200045v