4-(2-oxo-3-phenylquinoxalin-1(2H)-yl)butanoic acid | 1057226-68-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-(2-oxo-3-phenylquinoxalin-1(2H)-yl)butanoic acid
• 英文别名: 4-(2-Oxo-3-phenylquinoxalin-1-yl)butanoic acid
• CAS: 1057226-68-2
• 化学式: C₁₈H₁₆N₂O₃
• 分子量: 308.337
• InChiKey: NEKIAUOSPSWIRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-oxo-3-phenylquinoxalin-1(2H)-yl)butanoic acid 在 三甲基乙酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Prolyl Oligopeptidase Inhibition by N-Acyl-pro-pyrrolidine-type Molecules

  摘要：

  Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude.

  DOI：

  10.1021/jm800944x
• 作为产物：
  描述：

  ethyl 4-(2-oxo-3-phenylquinoxalin-1(2H)-yl)butanoate 在 盐酸 、 水 作用下， 反应 10.0h， 以57%的产率得到4-(2-oxo-3-phenylquinoxalin-1(2H)-yl)butanoic acid
  参考文献：
  名称：

  Prolyl Oligopeptidase Inhibition by N-Acyl-pro-pyrrolidine-type Molecules

  摘要：

  Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude.

  DOI：

  10.1021/jm800944x

文献信息

• Prolyl Oligopeptidase Inhibition by <i>N</i>-Acyl-pro-pyrrolidine-type Molecules
  作者：Károly Kánai、Péter Arányi、Zsolt Böcskei、György Ferenczy、Veronika Harmat、Kálmán Simon、Sándor Bátori、Gábor Náray-Szabó、István Hermecz

  DOI：10.1021/jm800944x

  日期：2008.12.11

  Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude.