2-(ethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester | 516490-63-4

• 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: 2-(ethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester
• 英文别名: Methyl 2-[ethyl-(2-methylphenyl)carbamoyl]cyclopent-2-ene-1-carboxylate
• CAS: 516490-63-4
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: JAAXYDWAOWBQEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  2-(ethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester 在 lithium hydroxide 、 三氟甲磺酸 、 苯甲醚 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 11.25h， 生成 Cyclopent-2-ene-1,2-dicarboxylic acid 1-(4-carbamimidoyl-benzylamide) 2-(ethyl-o-tolyl-amide)
  参考文献：
  名称：

  Synthesis of Novel Thrombin Inhibitors. Use of Ring-Closing Metathesis Reactions for Synthesis of P2 Cyclopentene- and Cyclohexenedicarboxylic Acid Derivatives

  摘要：

  The thrombin inhibitory tripeptide D-Phe-Pro-Arg has been mimicked using either cyclopentenedicarboxylic derivatives or a cyclohexenedicarboxylic derivative as surrogate for the P2 proline. In the P3 position, tertiary amides were optimized as D-Phe P3 replacements. The P1 arginine was, in all compounds, substituted with the more rigid and biocompatible 4-amino-methylbenzamidine. One of the novel inhibitors was cocrystallized with a-thrombin and subjected to X-ray analysis. From analysis of the X-ray crystal structure, new ligands were designed leading to significantly improved binding affinity, the lead candidate exhibiting an in vitro IC50 of 49 nM.

  DOI：

  10.1021/jm021065a
• 作为产物：
  描述：

  2-but-3-enyl-3-methylenesuccinic acid 1-methyl ester 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 2-(ethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of Novel Thrombin Inhibitors. Use of Ring-Closing Metathesis Reactions for Synthesis of P2 Cyclopentene- and Cyclohexenedicarboxylic Acid Derivatives

  摘要：

  The thrombin inhibitory tripeptide D-Phe-Pro-Arg has been mimicked using either cyclopentenedicarboxylic derivatives or a cyclohexenedicarboxylic derivative as surrogate for the P2 proline. In the P3 position, tertiary amides were optimized as D-Phe P3 replacements. The P1 arginine was, in all compounds, substituted with the more rigid and biocompatible 4-amino-methylbenzamidine. One of the novel inhibitors was cocrystallized with a-thrombin and subjected to X-ray analysis. From analysis of the X-ray crystal structure, new ligands were designed leading to significantly improved binding affinity, the lead candidate exhibiting an in vitro IC50 of 49 nM.

  DOI：

  10.1021/jm021065a