isophthalic acid mono(L-alanyl-pyrrolidine) amide | 485835-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: isophthalic acid mono(L-alanyl-pyrrolidine) amide
• 英文别名: 3-[[(2S)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl]carbamoyl]benzoic acid
• CAS: 485835-49-2
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: VUXPQKHTVWVRPD-JTQLQIEISA-N

物化性质

• 沸点：
  567.0±35.0 °C(Predicted)
• 密度：
  1.289±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  isophthalic acid mono(L-alanyl-pyrrolidine) amide 在 lithium hydroxide 、 三甲基乙酰氯 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 isophthalic acid L-alanyl-pyrrolidine L-proline amide
  参考文献：
  名称：

  New Prolyl Oligopeptidase Inhibitors Developed from Dicarboxylic Acid Bis(l-prolyl-pyrrolidine) Amides

  摘要：

  Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl. group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)(hydroxyacetyl)pyrrolidinyl groups.

  DOI：

  10.1021/jm030811o
• 作为产物：
  描述：

  methyl 3-[[(2S)-1-oxo-1-pyrrolidin-1-ylpropan-2-yl]carbamoyl]benzoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以1.9 g的产率得到isophthalic acid mono(L-alanyl-pyrrolidine) amide
  参考文献：
  名称：

  New Prolyl Oligopeptidase Inhibitors Developed from Dicarboxylic Acid Bis(l-prolyl-pyrrolidine) Amides

  摘要：

  Isophthalic acid bis(L-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl. group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)(hydroxyacetyl)pyrrolidinyl groups.

  DOI：

  10.1021/jm030811o