allylcarbamic acid biphenyl-3-yl ester | 1033694-29-9

• 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: allylcarbamic acid biphenyl-3-yl ester
• 英文别名: (3-phenylphenyl) N-prop-2-enylcarbamate
• CAS: 1033694-29-9
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: IVZVLOUIEAWCIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  间羟基联苯 、 3-异氰酸丙烯 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 9.0h， 以91%的产率得到allylcarbamic acid biphenyl-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

• Methods, Compositions, And Compounds For Modulation Of Monoacylglycerol Lipase, Pain, And Stress-Related Disorders
  申请人：Piomelli Daniele

  公开号：US20090082435A1

  公开（公告）日：2009-03-26

  Methods, compositions, and compounds for inhibiting monoacyglycerol lipase, and for treating pain, for modulating stress-induced analgesia or for treating stress-induced disorders in mammals are provided.
• [EN] METHODS, COMPOSITIONS, AND COMPOUNDS FOR MODULATION OF MONOACYLGLYCEROL LIPASE, PAIN, AND STRESS-RELATED DISORDERS<br/>[FR] PROCEDES, COMPOSITIONS ET COMPOSES DE MODULATION DE LA LIPASE DE MONOACYLGLYCEROL, DE DOULEURS ET DE TROUBLES LIES AU STRESS
  申请人：UNIV CALIFORNIA

  公开号：WO2006116773A2

  公开（公告）日：2006-11-02

  [EN] Methods, compositions, and compounds for inhibiting monoacyglycerol lipase, and for treating pain, for modulating stress-induced analgesia or for treating stress-induced disorders in mammals are provided.
  [FR] L'invention concerne des procédés, des compositions et des composés destinés à l'inhibition de la lipase de monoacyglycérol et au traitement de la douleur, à la modulation de l'analgésie induite par le stress ou au traitement de troubles induits par le stress chez les mammifères.
• 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.