2-but-3-enyl-3-methylenesuccinic acid 1-methyl ester | 516490-53-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-but-3-enyl-3-methylenesuccinic acid 1-methyl ester
• 英文别名: 3-Methoxycarbonyl-2-methylidenehept-6-enoic acid
• CAS: 516490-53-2
• 化学式: C₁₀H₁₄O₄
• 分子量: 198.219
• InChiKey: YVKNGIJCAVBUNX-UHFFFAOYSA-N

物化性质

• 沸点：
  326.9±42.0 °C(Predicted)
• 密度：
  1.088±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-溴-1-丁烯 、 衣康酸单甲酯 在 N,N-二甲基丙烯基脲 、 lithium diisopropyl amide 、 lithium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 20.5h， 以48%的产率得到2-but-3-enyl-3-methylenesuccinic acid 1-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

文献信息

• Synthesis of Novel Thrombin Inhibitors. Use of Ring-Closing Metathesis Reactions for Synthesis of P2 Cyclopentene- and Cyclohexenedicarboxylic Acid Derivatives
  作者：Fredrik Thorstensson、Ingemar Kvarnström、Djordje Musil、Ingemar Nilsson、Bertil Samuelsson

  DOI：10.1021/jm021065a

  日期：2003.3.1

  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.