UP57

• 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: UP57
• 英文别名: (5Z,8Z,11Z,14Z)-N-(4-methoxyphenyl)icosa-5,8,11,14-tetraenamide
• 化学式: C₂₇H₃₉NO₂
• 分子量: 409.612
• InChiKey: RAAXJIUKGYWMQD-ZKWNWVNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  30
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  花生四烯酸 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 UP57
  参考文献：
  名称：

  AM404 Analogs as Activators of the 20S Isoform of the Human Proteasome

  摘要：

  The proteasome is a multisubunit protease system responsible for the majority of the protein turnover in eukaryotic organisms. Dysregulation of this enzymatic complex leads to protein accumulation, subsequent aggregation, and ultimately diseased states; for that reason, positive modulation of its activity has been recently investigated as a therapeutic strategy for neurodegenerative and age‐related diseases. The small molecule AM404 was recently identified as an activator of the 20S isoform of the proteasome and further exploration of the scaffold revealed the importance of the polyunsaturated fatty acid chain to elicit activity. Herein, we report the investigation of the aromatic region of the scaffold and the evaluation of the small molecules in a variety of proteasome activity and protein degradation assays. We found that derivatives A22 and A23, compared to AM404, exhibit enhanced proteasome activity in biochemical and cellular proteasome assays and more favorable cellular viability profiles. Additionally, these compounds demonstrate the ability to degrade intrinsically disordered proteins, regardless of their molecular weight, and the ability to restore the proteasome activity in the presence of toxic oligomeric α‐Syn species in a biochemical setting.

  DOI：

  10.1002/cbic.202400284

文献信息

• New metabolically stable fatty acid amide ligands of cannabinoid receptors: Synthesis and receptor affinity studies
  作者：Paolo Urbani、Paolo Cavallo、Maria Grazia Cascio、Mariafrancesca Buonerba、Giovanni De Martino、Vincenzo Di Marzo、Carmela Saturnino

  DOI：10.1016/j.bmcl.2005.09.023

  日期：2006.1

  We investigated the structure-activity relationships for the interactions of fatty acid amide analogs of the endocannabinoid anandamide with human recombinant cannabinoid receptors. Thirty-five novel fatty acid amides were synthesized using five different types of acyl chains and 11 different aromatic amine 'heads.' Although none of the new compounds was a more potent ligand than anandamide, we identified

  我们调查了内源性大麻素南and酰胺的脂肪酸酰胺类似物与人重组大麻素受体相互作用的构效关系。使用五种不同类型的酰基链和11种不同的芳香胺“头”合成了35种新型脂肪酸酰胺。尽管没有一种新化合物比anandamide具有更强的配位体，但我们确定了三个能够改善花生四烯酰胺的代谢稳定性及其CB（1）/ CB（2）选择性比超过20倍的胺基，以及几种芳香族胺能够提高短链或单饱和脂肪酸对大麻素CB（1）受体的亲和力。首次发现花生四烯酸叔酰胺对大麻素CB（1）受体具有中等亲和力（K（i）= 300 nM），但对CB（2）受体不具有中等亲和力。