isophthalic acid (L-proline methyl ester) L-prolyl-pyrrolidine amide | 473797-85-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: isophthalic acid (L-proline methyl ester) L-prolyl-pyrrolidine amide
• 英文别名: methyl (2S)-1-[3-[(2S)-2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carbonyl]benzoyl]pyrrolidine-2-carboxylate
• CAS: 473797-85-2
• 化学式: C₂₃H₂₉N₃O₅
• 分子量: 427.5
• InChiKey: ASYAFOMKQHLDEF-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  87.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  isophthalic acid (L-proline methyl ester) L-prolyl-pyrrolidine amide 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以81%的产率得到isophthalic acid L-proline L-prolyl-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
• 作为产物：
  描述：

  间苯二甲酸单甲酯 在 lithium hydroxide 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 isophthalic acid (L-proline methyl ester) L-prolyl-pyrrolidine amide
  参考文献：
  名称：

  Dicarboxylic Acid bis(l-Prolyl-pyrrolidine) Amides as Prolyl Oligopeptidase Inhibitors

  摘要：

  New dicarboxylic acid bis(L-prolyl-pyrrolidine) amides were synthesized, and their inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. As compared with earlier described prolyl oligopeptidase inhibitors, these new compounds have in common an L-prolyl-pyrrolidine moiety, but the typical lipophilic acyl end group is replaced by another L-prolyl-pyrrolidine moiety connected symmetrically with a short dicarboxylic acid linker. These compounds are a new type of peptidomimetic prolyl oligopeptidase inhibitor.

  DOI：

  10.1021/jm020966g