Cyclopent-2-ene-1,2-dicarboxylic acid 1-(4-carbamimidoyl-benzylamide) 2-[(5-chloro-2-methyl-phenyl)-ethyl-amide]

• 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: Cyclopent-2-ene-1,2-dicarboxylic acid 1-(4-carbamimidoyl-benzylamide) 2-[(5-chloro-2-methyl-phenyl)-ethyl-amide]
• 英文别名: 1-N-[(4-carbamimidoylphenyl)methyl]-2-N-(5-chloro-2-methylphenyl)-2-N-ethylcyclopent-2-ene-1,2-dicarboxamide
• 化学式: C₂₄H₂₇ClN₄O₂
• 分子量: 438.957
• InChiKey: BOAPQIZSLVJDEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-chloro-N-ethyl-2-methylaniline 在 lithium hydroxide 、 三氟甲磺酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-羟基苯并三唑 、 苯甲醚 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 Cyclopent-2-ene-1,2-dicarboxylic acid 1-(4-carbamimidoyl-benzylamide) 2-[(5-chloro-2-methyl-phenyl)-ethyl-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

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.