4-[5-(tert-butoxycarbonyl)-2-furyl]benzoic acid | 937377-68-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃
• 英文名称: 4-[5-(tert-butoxycarbonyl)-2-furyl]benzoic acid
• 英文别名: 4-[5-[(2-Methylpropan-2-yl)oxycarbonyl]furan-2-yl]benzoic acid
• CAS: 937377-68-9
• 化学式: C₁₆H₁₆O₅
• 分子量: 288.3
• InChiKey: RJXRVHGVAJKGQO-UHFFFAOYSA-N

物化性质

• 沸点：
  457.0±40.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[5-(tert-butoxycarbonyl)-2-furyl]benzoic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 tert-butyl 5-(4-(chlorocarbonyl)phenyl)furan-2-carboxylate
  参考文献：
  名称：

  NMR Screening Applied to the Fragment-Based Generation of Inhibitors of Creatine Kinase Exploiting a New Interaction Proximate to the ATP Binding Site

  摘要：

  Using an in-house fragment NMR library, we identified a set of ligands that bind rabbit muscular creatine kinase, an enzyme involved in key ATP-dependent processes. The ligands docked to the crystal structures of creatine kinase indicated that a phenylfuroic acid could enter into a pocket adjacent to the nucleotide binding site. This fragment served as an anchor to develop in silico a series of potential inhibitors which could partly access the nucleotide binding site. The short synthesis of only four derivatives provided entirely novel hit compounds that reversibly inhibit creatine kinase at micromolar concentrations with a mixed ATP-competitive/noncompetitive mechanism in agreement with the structural model of the inhibited enzyme. These initial biologically active compounds are novel and modular and exploit a new interaction proximate to the ATP binding site.

  DOI：

  10.1021/jm061460r
• 作为产物：
  描述：

  tert-butyl 5-bromofuran-2-carboxylate 、 4-羧基苯硼酸 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 以74%的产率得到4-[5-(tert-butoxycarbonyl)-2-furyl]benzoic acid
  参考文献：
  名称：

  NMR Screening Applied to the Fragment-Based Generation of Inhibitors of Creatine Kinase Exploiting a New Interaction Proximate to the ATP Binding Site

  摘要：

  Using an in-house fragment NMR library, we identified a set of ligands that bind rabbit muscular creatine kinase, an enzyme involved in key ATP-dependent processes. The ligands docked to the crystal structures of creatine kinase indicated that a phenylfuroic acid could enter into a pocket adjacent to the nucleotide binding site. This fragment served as an anchor to develop in silico a series of potential inhibitors which could partly access the nucleotide binding site. The short synthesis of only four derivatives provided entirely novel hit compounds that reversibly inhibit creatine kinase at micromolar concentrations with a mixed ATP-competitive/noncompetitive mechanism in agreement with the structural model of the inhibited enzyme. These initial biologically active compounds are novel and modular and exploit a new interaction proximate to the ATP binding site.

  DOI：

  10.1021/jm061460r

文献信息

• NMR Screening Applied to the Fragment-Based Generation of Inhibitors of Creatine Kinase Exploiting a New Interaction Proximate to the ATP Binding Site
  作者：Anne-Sophie Bretonnet、Anne Jochum、Olivier Walker、Isabelle Krimm、Peter Goekjian、Olivier Marcillat、Jean-Marc Lancelin

  DOI：10.1021/jm061460r

  日期：2007.4.1

  Using an in-house fragment NMR library, we identified a set of ligands that bind rabbit muscular creatine kinase, an enzyme involved in key ATP-dependent processes. The ligands docked to the crystal structures of creatine kinase indicated that a phenylfuroic acid could enter into a pocket adjacent to the nucleotide binding site. This fragment served as an anchor to develop in silico a series of potential inhibitors which could partly access the nucleotide binding site. The short synthesis of only four derivatives provided entirely novel hit compounds that reversibly inhibit creatine kinase at micromolar concentrations with a mixed ATP-competitive/noncompetitive mechanism in agreement with the structural model of the inhibited enzyme. These initial biologically active compounds are novel and modular and exploit a new interaction proximate to the ATP binding site.