2-[(Z)-2-tri(propan-2-yl)silyloxyethenyl]isoindole-1,3-dione | 1152704-63-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[(Z)-2-tri(propan-2-yl)silyloxyethenyl]isoindole-1,3-dione
• CAS: 1152704-63-6
• 化学式: C₁₉H₂₇NO₃Si
• 分子量: 345.514
• InChiKey: BXZANYHOCKVYHT-QXMHVHEDSA-N

物化性质

• 沸点：
  395.9±44.0 °C(Predicted)
• 密度：
  1.101±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.95
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  二碘甲烷 、 2-[(Z)-2-tri(propan-2-yl)silyloxyethenyl]isoindole-1,3-dione 在 diethylzinc 作用下， 以 正己烷 、 苯 为溶剂， 以93%的产率得到
  参考文献：
  名称：

  Conformationally Constrained Fatty Acid Ethanolamides as Cannabinoid and Vanilloid Receptor Probes

  摘要：

  To investigate if certain acylethanolamides bind to both cannabinoid (CB(1) and CB(2)) and vanilloid TRPV1 receptors because of their conformational flexibility, we introduced a methylene lock on their ethanolamine "head", thereby generating a cyclopropane ring with two stereogenic centers and chiral cis/trans diastereomers with different topology of presentation to binding sites. After resolution by chiral-phase HPLC, diastereo-and enantiopure arachidonoyl-, oleoyl-, and palmitoylcyclopropanolamides were tested in assays of CB(1), CB(2), and TRPV1 activity. Diastereodifferentiation between pairs of cis-trans isomers was observed only for TRPV1 activity, with poor enantiodifferentiation. Methylenation introduced (i) CB(1) receptor affinity in oleoylethanolamide while increasing in a diastereoselective way its activity at TRPV1 and (ii) strong diastereoselective activity at TRPV1, but not cannabinoid, receptors in the otherwise inactive palmitoylethanolamide. These results show that the N-alkyl group of acylethanolamides has a different role in their interaction with cannabinoid and vanilloid receptors and that acylcyclopropanolamides qualify as CB(1)/TRPV1 "hybrids" of potential therapeutic utility.

  DOI：

  10.1021/jm900130m
• 作为产物：
  描述：

  苯二甲酰亚氨基乙醛 、 三异丙基硅基三氟甲磺酸酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以37%的产率得到2-[(E)-2-tri(propan-2-yl)silyloxyethenyl]isoindole-1,3-dione
  参考文献：
  名称：

  Conformationally Constrained Fatty Acid Ethanolamides as Cannabinoid and Vanilloid Receptor Probes

  摘要：

  To investigate if certain acylethanolamides bind to both cannabinoid (CB(1) and CB(2)) and vanilloid TRPV1 receptors because of their conformational flexibility, we introduced a methylene lock on their ethanolamine "head", thereby generating a cyclopropane ring with two stereogenic centers and chiral cis/trans diastereomers with different topology of presentation to binding sites. After resolution by chiral-phase HPLC, diastereo-and enantiopure arachidonoyl-, oleoyl-, and palmitoylcyclopropanolamides were tested in assays of CB(1), CB(2), and TRPV1 activity. Diastereodifferentiation between pairs of cis-trans isomers was observed only for TRPV1 activity, with poor enantiodifferentiation. Methylenation introduced (i) CB(1) receptor affinity in oleoylethanolamide while increasing in a diastereoselective way its activity at TRPV1 and (ii) strong diastereoselective activity at TRPV1, but not cannabinoid, receptors in the otherwise inactive palmitoylethanolamide. These results show that the N-alkyl group of acylethanolamides has a different role in their interaction with cannabinoid and vanilloid receptors and that acylcyclopropanolamides qualify as CB(1)/TRPV1 "hybrids" of potential therapeutic utility.

  DOI：

  10.1021/jm900130m

文献信息

• Conformationally Constrained Fatty Acid Ethanolamides as Cannabinoid and Vanilloid Receptor Probes
  作者：Giovanni Appendino、Alessia Ligresti、Alberto Minassi、Maria Grazia Cascio、Marco Allarà、Orazio Taglialatela-Scafati、Roger G. Pertwee、Luciano De Petrocellis、Vincenzo Di Marzo

  DOI：10.1021/jm900130m

  日期：2009.5.14

  To investigate if certain acylethanolamides bind to both cannabinoid (CB(1) and CB(2)) and vanilloid TRPV1 receptors because of their conformational flexibility, we introduced a methylene lock on their ethanolamine "head", thereby generating a cyclopropane ring with two stereogenic centers and chiral cis/trans diastereomers with different topology of presentation to binding sites. After resolution by chiral-phase HPLC, diastereo-and enantiopure arachidonoyl-, oleoyl-, and palmitoylcyclopropanolamides were tested in assays of CB(1), CB(2), and TRPV1 activity. Diastereodifferentiation between pairs of cis-trans isomers was observed only for TRPV1 activity, with poor enantiodifferentiation. Methylenation introduced (i) CB(1) receptor affinity in oleoylethanolamide while increasing in a diastereoselective way its activity at TRPV1 and (ii) strong diastereoselective activity at TRPV1, but not cannabinoid, receptors in the otherwise inactive palmitoylethanolamide. These results show that the N-alkyl group of acylethanolamides has a different role in their interaction with cannabinoid and vanilloid receptors and that acylcyclopropanolamides qualify as CB(1)/TRPV1 "hybrids" of potential therapeutic utility.