methyl-5-((3-(benzylcarbamoyl)-6-iodo-4-oxoquinolin-1(4H)-yl)methyl)-2-methoxybenzoate | 1616491-37-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl-5-((3-(benzylcarbamoyl)-6-iodo-4-oxoquinolin-1(4H)-yl)methyl)-2-methoxybenzoate
• 英文别名: Methyl 5-[[3-(benzylcarbamoyl)-6-iodo-4-oxoquinolin-1-yl]methyl]-2-methoxybenzoate；methyl 5-[[3-(benzylcarbamoyl)-6-iodo-4-oxoquinolin-1-yl]methyl]-2-methoxybenzoate
• CAS: 1616491-37-2
• 化学式: C₂₇H₂₃IN₂O₅
• 分子量: 582.395
• InChiKey: XFHULGWPIOSGHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-甲基水杨酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 、 氨 、 水 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 四氯化碳 、 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 7.17h， 生成 methyl-5-((3-(benzylcarbamoyl)-6-iodo-4-oxoquinolin-1(4H)-yl)methyl)-2-methoxybenzoate
  参考文献：
  名称：

  4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B

  摘要：

  Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  DOI：

  10.1016/j.bmc.2014.05.028