6-hydroxy-3-(1-(4-(6-methoxybenzo[d]thiazol-2-ylamino)-4-oxobutyl)-1H-1,2,3-triazol-4-yl)-2-m-tolylbenzofuran-5-carboxylic acid | 1262759-53-4

• 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: 6-hydroxy-3-(1-(4-(6-methoxybenzo[d]thiazol-2-ylamino)-4-oxobutyl)-1H-1,2,3-triazol-4-yl)-2-m-tolylbenzofuran-5-carboxylic acid
• 英文别名: 6-Hydroxy-3-(1-(4-(6-methoxybenzo[d]thiazol-2-ylamino)-4-oxobutyl)-1H-1,2,3-triazol-4-yl)-2-meta-tolylbenzofuran-5-carboxylic Acid；6-hydroxy-3-[1-[4-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-4-oxobutyl]triazol-4-yl]-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid
• CAS: 1262759-53-4
• 化学式: C₃₀H₂₅N₅O₆S
• 分子量: 583.624
• InChiKey: BEWNGQMBEVZWOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  181
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-甲氧基水杨酸甲酯 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 copper(ll) sulfate pentahydrate 、 L-ascorbic acid sodium salt 、 碘 、 chloroamine-T 、 potassium carbonate 、 三乙胺 、 sodium iodide 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 6.0h， 生成 6-hydroxy-3-(1-(4-(6-methoxybenzo[d]thiazol-2-ylamino)-4-oxobutyl)-1H-1,2,3-triazol-4-yl)-2-m-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

文献信息

• Inhibition of Lymphoid Tyrosine Phosphatase by Benzofuran Salicylic Acids
  作者：Torkel Vang、Yuli Xie、Wallace H. Liu、Dušica Vidović、Yidong Liu、Shuangding Wu、Deborah H. Smith、Alison Rinderspacher、Caty Chung、Gangli Gong、Tomas Mustelin、Donald W. Landry、Robert C. Rickert、Stephan C. Schürer、Shi-Xian Deng、Lutz Tautz

  DOI：10.1021/jm101004d

  日期：2011.1.27

  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.