3-(2(S)-benzoylpyrrolidine-1-carbonyl)-benzoic acid | 485835-36-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(2(S)-benzoylpyrrolidine-1-carbonyl)-benzoic acid
• CAS: 485835-36-7
• 化学式: C₁₉H₁₇NO₄
• 分子量: 323.348
• InChiKey: LJXIKWGWVNBVTD-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.87
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  74.68
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(2(S)-benzoylpyrrolidine-1-carbonyl)-benzoic acid 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 2(S)-benzoylpyrrolidine 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：

  3-(2(S)-benzoylpyrrolidine-1-carbonyl)-benzoic acid methyl ester 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以94%的产率得到3-(2(S)-benzoylpyrrolidine-1-carbonyl)-benzoic acid
  参考文献：
  名称：

  Conformationally rigid N-acyl-5-alkyl-l-prolyl-pyrrolidines as prolyl oligopeptidase inhibitors

  摘要：

  In the N-acyl-(L)-prolyl-pyrrolidine type of prolyl oligopeptidase inhibitors the L-prolyl group was replaced by different 5-alkyl-(L)-prolyl groups, resulting in a series of N-acyl-5-alkyl-(L)-prolyl-pyrrolidines. Since N-amides of 5-alkyl-(L)-prolines are conformationally more rigid than those of (L)-proline, the main objective was to make more rigid prolyl oligopeptidase inhibitors. In the series of compounds where the N-acyl group was a Boc group, the 5(R)-tert-butyl group increased the potency strongly. A similar effect was not observed for the 5(S)-tert-butyl group. In the series of compounds where the N-acyl group was a 4-phenylbutanoyl group, the 5(R)-tert-butyl, 5(R)-methyl and 5(S)-methyl groups did not have an effect on the potency [the 5(S)-tert-butyl group was not tested in this series]. As an additional effect, the 5-tert-butyl groups increased the log P of the compounds 1.5 log units, which might be beneficial when targeting the compounds to the brain. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00363-8