4-((diethylcarbamoyl)oxy)benzoic acid | 1204297-93-7

• 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: 4-((diethylcarbamoyl)oxy)benzoic acid
• 英文别名: 4-[(Diethylcarbamoyl)oxy]benzoic acid；4-(diethylcarbamoyloxy)benzoic acid
• CAS: 1204297-93-7
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: DGPAUSSMVIDYGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((diethylcarbamoyl)oxy)benzoic acid 在 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 [4-[[3-(phenylcarbamoyl)phenyl]carbamoyl]phenyl] N,N-diethylcarbamate
  参考文献：
  名称：

  Di-aryl Sulfonamide Motif Adds π-Stacking Bulk in Negative Allosteric Modulators of the NMDA Receptor

  摘要：

  The N-methyl-D-aspartate receptor plays a critical role in central nervous system processes. Its diverse properties, as well as hypothesized role in neurological disease, render NMDA receptors a target of interest for the development of therapeutically relevant modulators. A number of subunit-selective modulators have been reported in the literature, one of which is TCN-201, a G1uN2A-selective negative allosteric modulator. Recently, it was determined from a cocrystallization study of TCN-201 with the NMDA receptor that a unique active pose exists in which the sulfonamide group of TCN-201 incorporates a pi-pi r stacking interaction between the two adjacent aryl rings that allows it to make important contacts with the protein. This finding led us to investigate whether this unique structural feature of the diaryl sulfonamide could be incorporated into other modulators that act on distinct pockets. To test whether this idea might have more general utility, we added an aryl ring plus the sulfonamide linker modification to a previously published series of G1uN2C- and G1uN2D-selective negative allosteric modulators that bind to an entirely different pocket. Herein, we report data suggesting that this structural modification of the NAB-14 series of modulators was tolerated and, in some instances, enhanced potency. These results suggest that this motif may be a reliable means for introducing a pi-pi stacking element to molecular scaffolds that could improve activity if it allowed access to ligand protein interactions not accessible from one planar aromatic group.

  DOI：

  10.1021/acsmedchemlett.8b00395
• 作为产物：
  描述：

  4-(methoxycarbonyl)phenyl N,N-diethylcarbamate 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以6.25 g的产率得到4-((diethylcarbamoyl)oxy)benzoic acid
  参考文献：
  名称：

  Di-aryl Sulfonamide Motif Adds π-Stacking Bulk in Negative Allosteric Modulators of the NMDA Receptor

  摘要：

  The N-methyl-D-aspartate receptor plays a critical role in central nervous system processes. Its diverse properties, as well as hypothesized role in neurological disease, render NMDA receptors a target of interest for the development of therapeutically relevant modulators. A number of subunit-selective modulators have been reported in the literature, one of which is TCN-201, a G1uN2A-selective negative allosteric modulator. Recently, it was determined from a cocrystallization study of TCN-201 with the NMDA receptor that a unique active pose exists in which the sulfonamide group of TCN-201 incorporates a pi-pi r stacking interaction between the two adjacent aryl rings that allows it to make important contacts with the protein. This finding led us to investigate whether this unique structural feature of the diaryl sulfonamide could be incorporated into other modulators that act on distinct pockets. To test whether this idea might have more general utility, we added an aryl ring plus the sulfonamide linker modification to a previously published series of G1uN2C- and G1uN2D-selective negative allosteric modulators that bind to an entirely different pocket. Herein, we report data suggesting that this structural modification of the NAB-14 series of modulators was tolerated and, in some instances, enhanced potency. These results suggest that this motif may be a reliable means for introducing a pi-pi stacking element to molecular scaffolds that could improve activity if it allowed access to ligand protein interactions not accessible from one planar aromatic group.

  DOI：

  10.1021/acsmedchemlett.8b00395

文献信息

• Di-aryl Sulfonamide Motif Adds π-Stacking Bulk in Negative Allosteric Modulators of the NMDA Receptor
  作者：Samantha L. Summer、Steven A. Kell、Zongjian Zhu、Rhonda Moore、Dennis C. Liotta、Scott J. Myers、George W. Koszalka、Stephen F. Traynelis、David S. Menaldino

  DOI：10.1021/acsmedchemlett.8b00395

  日期：2019.3.14

  The N-methyl-D-aspartate receptor plays a critical role in central nervous system processes. Its diverse properties, as well as hypothesized role in neurological disease, render NMDA receptors a target of interest for the development of therapeutically relevant modulators. A number of subunit-selective modulators have been reported in the literature, one of which is TCN-201, a G1uN2A-selective negative allosteric modulator. Recently, it was determined from a cocrystallization study of TCN-201 with the NMDA receptor that a unique active pose exists in which the sulfonamide group of TCN-201 incorporates a pi-pi r stacking interaction between the two adjacent aryl rings that allows it to make important contacts with the protein. This finding led us to investigate whether this unique structural feature of the diaryl sulfonamide could be incorporated into other modulators that act on distinct pockets. To test whether this idea might have more general utility, we added an aryl ring plus the sulfonamide linker modification to a previously published series of G1uN2C- and G1uN2D-selective negative allosteric modulators that bind to an entirely different pocket. Herein, we report data suggesting that this structural modification of the NAB-14 series of modulators was tolerated and, in some instances, enhanced potency. These results suggest that this motif may be a reliable means for introducing a pi-pi stacking element to molecular scaffolds that could improve activity if it allowed access to ligand protein interactions not accessible from one planar aromatic group.