isophthalic acid monomethyl ester azepane amide | 485836-38-2

• 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 monomethyl ester azepane amide
• 英文别名: Methyl 3-(azepane-1-carbonyl)benzoate
• CAS: 485836-38-2
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: WCWZZSJTCUZVEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  isophthalic acid monomethyl ester azepane 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 2.0h， 生成 (S)-1-{(S)-1-[3-(Azepane-1-carbonyl)-benzoyl]-pyrrolidine-2-carbonyl}-pyrrolidine-2-carbonitrile
  参考文献：
  名称：

  Dicarboxylic Acid Azacycle l-Prolyl-pyrrolidine Amides as Prolyl Oligopeptidase Inhibitors and Three-Dimensional Quantitative Structure−Activity Relationship of the Enzyme−Inhibitor Interactions

  摘要：

  A series of dicarboxylic acid azacycle L-prolyl-pyrrolidine amides was synthesized, and their inhibitory activity against prolyl oligopeptidase (POP) from porcine brain was tested. Three different azacycles were tested at the position beyond P3 and six different dicarboxylic acids at the P3 position. L-Prolyl-pyrrolidine and L-prolyl-2(S)-cyanopyrrolidine were used at the P2-P1 positions. The IC50 values ranged from 0.39 to 19000 nM. The most potent inhibitor was the 3,3-dimethylglutaric acid azepane L-prolyl-2(S)-cyanopyrrolidine amide. Molecular docking (GOLD) was used to analyze binding interactions between different POP inhibitors of this type and the POP enzyme. The data set consisted of the novel inhibitors, inhibitors published previously by our group, and well-known reference compounds. The alignments were further analyzed using comparative molecular similarity indices analysis. The binding of the inhibitors was consistent at the P1-P3 positions. Beyond the P3 position, two different binding modes were found, one that favors lipophilic structures and one that favors nonhydrophobic structures.

  DOI：

  10.1021/jm0500020
• 作为产物：
  描述：

  环己亚胺 、 间苯二甲酸单甲酯 在 三甲基乙酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以62%的产率得到isophthalic acid monomethyl ester azepane amide
  参考文献：
  名称：

  Dicarboxylic Acid Azacycle l-Prolyl-pyrrolidine Amides as Prolyl Oligopeptidase Inhibitors and Three-Dimensional Quantitative Structure−Activity Relationship of the Enzyme−Inhibitor Interactions

  摘要：

  A series of dicarboxylic acid azacycle L-prolyl-pyrrolidine amides was synthesized, and their inhibitory activity against prolyl oligopeptidase (POP) from porcine brain was tested. Three different azacycles were tested at the position beyond P3 and six different dicarboxylic acids at the P3 position. L-Prolyl-pyrrolidine and L-prolyl-2(S)-cyanopyrrolidine were used at the P2-P1 positions. The IC50 values ranged from 0.39 to 19000 nM. The most potent inhibitor was the 3,3-dimethylglutaric acid azepane L-prolyl-2(S)-cyanopyrrolidine amide. Molecular docking (GOLD) was used to analyze binding interactions between different POP inhibitors of this type and the POP enzyme. The data set consisted of the novel inhibitors, inhibitors published previously by our group, and well-known reference compounds. The alignments were further analyzed using comparative molecular similarity indices analysis. The binding of the inhibitors was consistent at the P1-P3 positions. Beyond the P3 position, two different binding modes were found, one that favors lipophilic structures and one that favors nonhydrophobic structures.

  DOI：

  10.1021/jm0500020