naphthalen-2-ylmethylcarbamic acid 3'-acetylbiphenyl-3-yl ester | 1033694-50-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: naphthalen-2-ylmethylcarbamic acid 3'-acetylbiphenyl-3-yl ester
• 英文别名: Naphthalen-2-ylmethylcarbamic Acid 3''-Acetylbiphenyl-3-yl Ester；[3-(3-acetylphenyl)phenyl] N-(naphthalen-2-ylmethyl)carbamate
• CAS: 1033694-50-6
• 化学式: C₂₆H₂₁NO₃
• 分子量: 395.458
• InChiKey: WCLPWHSEFYFKFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-萘基甲基异氰酸酯 、 1-[3-(3-羟基苯基)苯基]乙酮 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 7.0h， 以20%的产率得到naphthalen-2-ylmethylcarbamic acid 3'-acetylbiphenyl-3-yl ester
  参考文献：
  名称：

  Synthesis and Quantitative Structure−Activity Relationship of Fatty Acid Amide Hydrolase Inhibitors: Modulation at the N-Portion of Biphenyl-3-yl Alkylcarbamates

  摘要：

  Alkylcarbamic acid biphenyl-3-yl esters are a class of fatty acid amide hydrolase (FAAH) inhibitors that comprises cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester (URB597), a compound with analgesic, anxiolytic-like and antidepressant-like properties in rat and mouse models. Here, we extended the structure-activity relationships (SARs) for this class of compounds by replacing the cyclohexyl ring of the parent compound cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) (FAAH IC50 = 63 nM) with a selected set of substituents of different size, shape, flexibility, and lipophilicity. Docking experiments and linear interaction energy (LIE) calculations indicated that the N-terminal group of O-arylcarbamates fits within the lipophilic region of the substrate-binding site, mimicking the arachidonoyl chain of anandamide. Significant potency improvements were observed for the beta-naphthylmethyl derivative 4q (IC50 = 5.3 nM) and its 3'-carbamoylbiphenyl-3-yl ester 4z (URB880, IC50 = 0.63 nM), indicating that shape complementarity and hydrogen bonds are crucial to obtain highly potent inhibitors.

  DOI：

  10.1021/jm701631z

文献信息

• Synthesis and Quantitative Structure−Activity Relationship of Fatty Acid Amide Hydrolase Inhibitors: Modulation at the N-Portion of Biphenyl-3-yl Alkylcarbamates
  作者：Marco Mor、Alessio Lodola、Silvia Rivara、Federica Vacondio、Andrea Duranti、Andrea Tontini、Silvano Sanchini、Giovanni Piersanti、Jason R. Clapper、Alvin R. King、Giorgio Tarzia、Daniele Piomelli

  DOI：10.1021/jm701631z

  日期：2008.6.1

  Alkylcarbamic acid biphenyl-3-yl esters are a class of fatty acid amide hydrolase (FAAH) inhibitors that comprises cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester (URB597), a compound with analgesic, anxiolytic-like and antidepressant-like properties in rat and mouse models. Here, we extended the structure-activity relationships (SARs) for this class of compounds by replacing the cyclohexyl ring of the parent compound cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) (FAAH IC50 = 63 nM) with a selected set of substituents of different size, shape, flexibility, and lipophilicity. Docking experiments and linear interaction energy (LIE) calculations indicated that the N-terminal group of O-arylcarbamates fits within the lipophilic region of the substrate-binding site, mimicking the arachidonoyl chain of anandamide. Significant potency improvements were observed for the beta-naphthylmethyl derivative 4q (IC50 = 5.3 nM) and its 3'-carbamoylbiphenyl-3-yl ester 4z (URB880, IC50 = 0.63 nM), indicating that shape complementarity and hydrogen bonds are crucial to obtain highly potent inhibitors.