benzyl 4-(hydroxydinaphthalen-2-ylmethyl)piperidine-1-carboxylate | 1209468-80-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: benzyl 4-(hydroxydinaphthalen-2-ylmethyl)piperidine-1-carboxylate
• 英文别名: Benzyl 4-[hydroxy(dinaphthalen-2-yl)methyl]piperidine-1-carboxylate
• CAS: 1209468-80-3
• 化学式: C₃₄H₃₁NO₃
• 分子量: 501.625
• InChiKey: XJVMAGGJFIJMQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 4-(hydroxydinaphthalen-2-ylmethyl)piperidine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Characterization of Tunable Piperidine and Piperazine Carbamates as Inhibitors of Endocannabinoid Hydrolases

  摘要：

  Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes froth the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and anandamide, respectively. We have recently discovered that MAGL and FAAH arc both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CBI-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-membered ring to maintain potency.

  DOI：

  10.1021/jm9016976
• 作为产物：
  描述：

  2-溴萘 、 1-Cbz-哌啶-4-甲酸乙酯 在 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 4.5h， 以44%的产率得到benzyl 4-(hydroxydinaphthalen-2-ylmethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Characterization of Tunable Piperidine and Piperazine Carbamates as Inhibitors of Endocannabinoid Hydrolases

  摘要：

  Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes froth the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and anandamide, respectively. We have recently discovered that MAGL and FAAH arc both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CBI-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-membered ring to maintain potency.

  DOI：

  10.1021/jm9016976

文献信息

• Characterization of Tunable Piperidine and Piperazine Carbamates as Inhibitors of Endocannabinoid Hydrolases
  作者：Jonathan Z. Long、Xin Jin、Alexander Adibekian、Weiwei Li、Benjamin F. Cravatt

  DOI：10.1021/jm9016976

  日期：2010.2.25

  Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) are two enzymes froth the serine hydrolase superfamily that degrade the endocannabinoids 2-arachidonoylglycerol and anandamide, respectively. We have recently discovered that MAGL and FAAH arc both inhibited by carbamates bearing an N-piperidine/piperazine group. Piperidine/piperazine carbamates show excellent in vivo activity, raising brain endocannabinoid levels and producing CBI-dependent behavioral effects in mice, suggesting that they represent a promising class of inhibitors for studying the endogenous functions of MAGL and FAAH. Herein, we disclose a full account of the syntheses, structure-activity relationships, and inhibitory activities of piperidine/piperazine carbamates against members of the serine hydrolase family. These scaffolds can be tuned for MAGL-selective or dual MAGL-FAAH inhibition by the attachment of an appropriately substituted bisarylcarbinol or aryloxybenzyl moiety, respectively, on the piperidine/piperazine ring. Modifications to the piperidine/piperazine ring ablated inhibitory activity, suggesting a strict requirement for a six-membered ring to maintain potency.