cyclohex-2-ene-1,2-dicarboxylic acid 1-methyl ester | 516490-55-4

• 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: cyclohex-2-ene-1,2-dicarboxylic acid 1-methyl ester
• 英文别名: 6-Methoxycarbonylcyclohexene-1-carboxylic acid
• CAS: 516490-55-4
• 化学式: C₉H₁₂O₄
• 分子量: 184.192
• InChiKey: AHKUAFNWSYYWPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  cyclohex-2-ene-1,2-dicarboxylic acid 1-methyl ester 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 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 27.5h， 生成 cyclohex-2-ene-1,2-dicarboxylic acid 1-(4-carbamimidoyl-benzylamide) 2-phenylamide
  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：

  衣康酸单甲酯 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) N,N-二甲基丙烯基脲 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 60.5h， 生成 cyclohex-2-ene-1,2-dicarboxylic 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

• Exploring the Active Conformation of Cyclohexane Carboxylate Positive Allosteric Modulators of the Type 4 Metabotropic Glutamate Receptor
  作者：Xavier Rovira、Youssef Harrak、Ana Trapero、Patricia González-Bulnes、Fanny Malhaire、Jean-Philippe Pin、Cyril Goudet、Jesús Giraldo、Amadeu Llebaria

  DOI：10.1002/cmdc.201402190

  日期：2014.12

  The active conformation of a family of metabotropic glutamate receptor subtype 4 (mGlu4) positive allosteric modulators (PAMs) with the cyclohexane 1,2‐dicarboxylic scaffold present in cis‐2‐(3,5‐dichlorophenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041) was investigated by testing structurally similar six‐membered ring compounds that have a locked conformation. The norbornane and cyclohexane molecules

  一个代谢型谷氨酸受体亚型4（mGlu 4）阳性变构调节剂（PAM）家族的活性构型与顺式-2-（3,5-二氯苯基氨基甲酰基）环己烷羧酸（VU0155041）中存在的环己烷1,2-二羧酸骨架相符通过测试结构相似的具有锁定构象的六元环化合物进行了研究。设计成组mGlu降冰片烷和环己烷分子4个构象探针和对映异构体的反式非对映体进行了计算，其特征在于和组mGlu测试4药理分析。结果支持VU0155041活性构象，其中椅子环己烷在轴向位置具有芳族酰胺取代基并且在赤道位置具有羧酸盐。此外，该受体显示出手性PAM的对映体鉴别。所构建的药效团具有高度受限的mGlu 4变构结合位点，因此为mGlu 4 PAM的基于结构的药物设计迈出了一步。