methyl 6-acetoxy-2-(4-methylphenyl)-3-((trimethylsilyl)ethynyl)benzofuran-5-carboxylate | 1262759-44-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: methyl 6-acetoxy-2-(4-methylphenyl)-3-((trimethylsilyl)ethynyl)benzofuran-5-carboxylate
• 英文别名: Methyl 6-acetyloxy-2-(4-methylphenyl)-3-(2-trimethylsilylethynyl)-1-benzofuran-5-carboxylate
• CAS: 1262759-44-3
• 化学式: C₂₄H₂₄O₅Si
• 分子量: 420.537
• InChiKey: KGMWACVUWIRVFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.35
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 6-acetoxy-2-(4-methylphenyl)-3-((trimethylsilyl)ethynyl)benzofuran-5-carboxylate 在 甲醇 、 copper(ll) sulfate pentahydrate 、 L-ascorbic acid sodium salt 、 potassium carbonate 、 lithium hydroxide 作用下， 以 甲醇 、 水 、 叔丁醇 为溶剂， 反应 25.0h， 生成 6-hydroxy-3-(1-(6-(naphthalen-1-ylamino)-6-oxohexyl)-1H-1,2,3-triazol-4-yl)-2-para-tolylbenzofuran-5-carboxylic acid
  参考文献：
  名称：

  Inhibition of Lymphoid Tyrosine Phosphatase by Benzofuran Salicylic Acids

  摘要：

  The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune diseases, including type I diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Since the disease-associated allele is a more potent inhibitor of TCR signaling, specific Lyp inhibitors May become valuable in treating autoimmunity. Using a structure-based approach, we synthesized a library of 34 compounds that inhibited Lyp with IC50 values between 0.27 and 6.2 mu M. A reporter assay was employed to screen for compounds that enhanced TCR signaling in cells, and several inhibitors displayed a dose-dependent, activating effect. Subsequent probing for Lyp's direct physiological targets by immunoblot analysis confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity profiling against closely related tyrosine phosphatases and in silico docking studies with the crystal structure of Lyp yielded valuable information for the design of Lyp-specific compounds.

  DOI：

  10.1021/jm101004d
• 作为产物：
  描述：

  methyl 2-acetoxy-4-methoxy-5-((4-methylphenyl)ethynylbenzoate) 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 碘 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 6-acetoxy-2-(4-methylphenyl)-3-((trimethylsilyl)ethynyl)benzofuran-5-carboxylate
  参考文献：
  名称：

  Inhibition of Lymphoid Tyrosine Phosphatase by Benzofuran Salicylic Acids

  摘要：

  The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune diseases, including type I diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Since the disease-associated allele is a more potent inhibitor of TCR signaling, specific Lyp inhibitors May become valuable in treating autoimmunity. Using a structure-based approach, we synthesized a library of 34 compounds that inhibited Lyp with IC50 values between 0.27 and 6.2 mu M. A reporter assay was employed to screen for compounds that enhanced TCR signaling in cells, and several inhibitors displayed a dose-dependent, activating effect. Subsequent probing for Lyp's direct physiological targets by immunoblot analysis confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity profiling against closely related tyrosine phosphatases and in silico docking studies with the crystal structure of Lyp yielded valuable information for the design of Lyp-specific compounds.

  DOI：

  10.1021/jm101004d