(-)-S-2-(4-bromo-phenoxy)-2-methylbutanoic acid | 1229447-51-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (-)-S-2-(4-bromo-phenoxy)-2-methylbutanoic acid
• 英文别名: (2S)-2-(4-bromophenoxy)-2-methylbutanoic acid
• CAS: 1229447-51-1
• 化学式: C₁₁H₁₃BrO₃
• 分子量: 273.126
• InChiKey: JNWUSQKIABEOIC-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 (-)-S-2-(4-bromo-phenoxy)-2-methylbutanoic acid 在 硫酸 作用下， 反应 3.0h， 以89%的产率得到(-)-S-methyl 2-(4-bromo-phenoxy)-2-methylbutanoate
  参考文献：
  名称：

  Structural Insight into Peroxisome Proliferator-Activated Receptor γ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis

  摘要：

  Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPAR gamma. The partial agonism of the Senantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPAR gamma regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPAR gamma coactivator 1 alpha (PGC-1 alpha) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPAR gamma, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPAR gamma. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants.

  DOI：

  10.1021/jm9013899
• 作为产物：
  描述：

  在 盐酸 作用下， 以 乙醚 、 水 为溶剂， 反应 0.5h， 以1.51 g的产率得到(-)-S-2-(4-bromo-phenoxy)-2-methylbutanoic acid
  参考文献：
  名称：

  Structural Insight into Peroxisome Proliferator-Activated Receptor γ Binding of Two Ureidofibrate-Like Enantiomers by Molecular Dynamics, Cofactor Interaction Analysis, and Site-Directed Mutagenesis

  摘要：

  Molecular dynamics simulations were performed on two ureidofibrate-like enantiomers to gain insight into their different potency and efficacy against PPAR gamma. The partial agonism of the Senantiomer seems to be due to its capability to stabilize different regions of the receptor allowing the interaction with both coactivators and corepressors as shown by fluorescence resonance energy transfer (FRET) assays. The recruitment of the corepressor N-CoR1 by the S enantiomer on two different responsive elements of PPAR gamma regulated promoters was confirmed by chromatin immunoprecipitation assays. Cell-based transcription assays show that PPAR gamma coactivator 1 alpha (PGC-1 alpha) and cAMP response element binding protein-binding protein (CBP) enhance the basal and ligand-stimulated receptor activity acting as coactivators of PPAR gamma, whereas the receptor interacting protein 140 (RIP140) and the nuclear corepressor 1 (N-CoR1) repress the transcriptional activity of PPAR gamma. We also tested the importance of the residue Q286 on the transcriptional activity of the receptor by site-directed mutagenesis and confirmed its key role in the stabilization of helix 12. Molecular modeling studies were performed to provide a molecular explanation for the different behavior of the mutants.

  DOI：

  10.1021/jm9013899