2-(tert-butoxycarbonylmethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester | 516490-66-7

• 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: 2-(tert-butoxycarbonylmethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester
• 英文别名: Methyl 2-[(2-methylphenyl)-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]carbamoyl]cyclopent-2-ene-1-carboxylate
• CAS: 516490-66-7
• 化学式: C₂₁H₂₇NO₅
• 分子量: 373.449
• InChiKey: XZGGMHXKQXPGEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(tert-butoxycarbonylmethyl-o-tolylcarbamoyl)cyclopent-2-enecarboxylic acid methyl ester 在 lithium hydroxide 、 三氟甲磺酸 、 1-羟基苯并三唑 、 苯甲醚 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 11.25h， 生成 {[5-(4-Carbamimidoyl-benzylcarbamoyl)-cyclopent-1-enecarbonyl]-o-tolyl-amino}-acetic acid
  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：

  溴乙酸叔丁酯 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 21.08h， 生成 2-(tert-butoxycarbonylmethyl-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