(4-hydroxy-3-methylphenyl)(5-hydroxybenzo[b]thiophen-2-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-hydroxy-3-methylphenyl)(5-hydroxybenzo[b]thiophen-2-yl)methanone
• 英文别名: (5-Hydroxy-1-benzothiophen-2-yl)-(4-hydroxy-3-methylphenyl)methanone；(5-hydroxy-1-benzothiophen-2-yl)-(4-hydroxy-3-methylphenyl)methanone
• 化学式: C₁₆H₁₂O₃S
• 分子量: 284.335
• InChiKey: WRKBHVDIKMUHFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  85.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基-3-甲基苯乙酮 在 水 、 potassium carbonate 、 sodium hydrogensulfite 、 copper(ll) bromide 作用下， 以 氯仿 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 52.5h， 生成 (4-hydroxy-3-methylphenyl)(5-hydroxybenzo[b]thiophen-2-yl)methanone
  参考文献：
  名称：

  Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4

  摘要：

  Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosphorylation. This provides an option for the pharmacological correction of aberrant splicing by inhibiting the relevant kinases. Cdc2-like kinases (Clks) and dual specificity tyrosine phosphorylation-regulated kinases (Dyrks) were both reported to phosphorylate numerous SR proteins in vitro and in vivo. In this study, we describe the discovery of new selective dual Clk/Dyrk1A/1B inhibitors, which are able to modulate alternative pre-mRNA splicing of model gene transcripts in cells with submicromolar potencies. The optimization process yielded a dual Clk and Dyrk inhibitor with exceptionally high ligand efficiency. Our results suggested that dual inhibition of both Clk1 and Dyrk1A increased the efficacy of pre-mRNA splicing modulation.

  DOI：

  10.1021/ml500059y

文献信息

• Hydroxybenzothiophene Ketones Are Efficient Pre-mRNA Splicing Modulators Due to Dual Inhibition of Dyrk1A and Clk1/4
  作者：Christian Schmitt、Parisa Miralinaghi、Marica Mariano、Rolf W. Hartmann、Matthias Engel

  DOI：10.1021/ml500059y

  日期：2014.9.11

  Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosphorylation. This provides an option for the pharmacological correction of aberrant splicing by inhibiting the relevant kinases. Cdc2-like kinases (Clks) and dual specificity tyrosine phosphorylation-regulated kinases (Dyrks) were both reported to phosphorylate numerous SR proteins in vitro and in vivo. In this study, we describe the discovery of new selective dual Clk/Dyrk1A/1B inhibitors, which are able to modulate alternative pre-mRNA splicing of model gene transcripts in cells with submicromolar potencies. The optimization process yielded a dual Clk and Dyrk inhibitor with exceptionally high ligand efficiency. Our results suggested that dual inhibition of both Clk1 and Dyrk1A increased the efficacy of pre-mRNA splicing modulation.