3-[3-(羟基甲基)苯基]苯酚 | 176212-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-[3-(羟基甲基)苯基]苯酚
• 中文别名: 2(5H)-异噻唑甲酰胺,N,3-二甲基-4-(1-甲基乙基)-N-[(4-甲基苯基)甲基]-5-羰基-
• 英文名称: 3'-hydoxymethylbiphenyl-3-ol
• 英文别名: 3'-(Hydroxymethyl)[1,1'-biphenyl]-3-ol；3-[3-(hydroxymethyl)phenyl]phenol
• CAS: 176212-54-7
• 化学式: C₁₃H₁₂O₂
• 分子量: 200.237
• InChiKey: IYFICUQEHAUKMS-UHFFFAOYSA-N

物化性质

• 沸点：
  408.6±33.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  环己基异氰酸酯 、 3-[3-(羟基甲基)苯基]苯酚 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以64%的产率得到Cyclohexyl-carbamic acid 3''''-hydroxymethyl-biphenyl-3-yl ester
  参考文献：
  名称：

  Cyclohexylcarbamic Acid 3‘- or 4‘-Substituted Biphenyl-3-yl Esters as Fatty Acid Amide Hydrolase Inhibitors:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling Studies

  摘要：

  Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester URB524 (half-maximal inhibitory concentration, IC50 = 63 nM), which have significant anxiolytic-like properties in rats. In the present study, by introducing a selected group of substituents at the meta and para positions of the distal phenyl ring of URB524, we have characterized structure-activity profiles for this series of compounds and shown that introduction of small polar groups in the meta position greatly improves inhibitory potency. Most potent in the series was the m-carbamoyl derivative URB597 (4i, IC50 = 4.6 nM). Furthermore, quantitative structure-activity relationship (QSAR) analysis of an extended set of meta-substituted derivatives revealed a negative correlation between potency and lipophilicity and suggested that small-sized substituents may undertake polar interactions with the binding pocket of the enzyme. Docking studies and molecular dynamics simulations, using the crystal structure of FAAH, indicated that the O-biphenyl scaffold of the carbamate inhibitors can be accommodated within a lipophilic region of the substrate-binding site, where their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the meta position of the distal. phenyl ring can form hydrogen bonds with atoms located on the polar section of a narrow channel pointing toward the membrane-associated side of the enzyme. The structure-activity characterization reported here should help optimize the pharmacodynamic and pharmacokinetic properties of this class of compounds.

  DOI：

  10.1021/jm031140x
• 作为产物：
  描述：

  3-溴苯甲醇 、 3-羟基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 1.0h， 以92%的产率得到3-[3-(羟基甲基)苯基]苯酚
  参考文献：
  名称：

  Cyclohexylcarbamic Acid 3‘- or 4‘-Substituted Biphenyl-3-yl Esters as Fatty Acid Amide Hydrolase Inhibitors:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling Studies

  摘要：

  Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester URB524 (half-maximal inhibitory concentration, IC50 = 63 nM), which have significant anxiolytic-like properties in rats. In the present study, by introducing a selected group of substituents at the meta and para positions of the distal phenyl ring of URB524, we have characterized structure-activity profiles for this series of compounds and shown that introduction of small polar groups in the meta position greatly improves inhibitory potency. Most potent in the series was the m-carbamoyl derivative URB597 (4i, IC50 = 4.6 nM). Furthermore, quantitative structure-activity relationship (QSAR) analysis of an extended set of meta-substituted derivatives revealed a negative correlation between potency and lipophilicity and suggested that small-sized substituents may undertake polar interactions with the binding pocket of the enzyme. Docking studies and molecular dynamics simulations, using the crystal structure of FAAH, indicated that the O-biphenyl scaffold of the carbamate inhibitors can be accommodated within a lipophilic region of the substrate-binding site, where their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the meta position of the distal. phenyl ring can form hydrogen bonds with atoms located on the polar section of a narrow channel pointing toward the membrane-associated side of the enzyme. The structure-activity characterization reported here should help optimize the pharmacodynamic and pharmacokinetic properties of this class of compounds.

  DOI：

  10.1021/jm031140x

文献信息

• [EN] CARBOXAMIDE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE CARBOXAMIDE EN TANT QU'ANTAGONISTES DE RECEPTEUR MUSCARINIQUE
  申请人：PFIZER LTD

  公开号：WO2007034325A1

  公开（公告）日：2007-03-29

  [EN] The invention relates to compounds of Formula (I) processes and intermediates for their preparation, their use as muscarinic antagonists and pharmaceutical composition containing them.
  [FR] La présente invention a trait à des composés de formule (I), à des procédés et des intermédiaires pour leur préparation, à leur utilisation en tant qu'antagonistes muscariniques et à des compositions pharmaceutiques les contenant.
• Cyclohexylcarbamic Acid 3‘- or 4‘-Substituted Biphenyl-3-yl Esters as Fatty Acid Amide Hydrolase Inhibitors:  Synthesis, Quantitative Structure−Activity Relationships, and Molecular Modeling Studies
  作者：Marco Mor、Silvia Rivara、Alessio Lodola、Pier Vincenzo Plazzi、Giorgio Tarzia、Andrea Duranti、Andrea Tontini、Giovanni Piersanti、Satish Kathuria、Daniele Piomelli

  DOI：10.1021/jm031140x

  日期：2004.10.1

  Fatty acid amide hydrolase (FAAH) is a promising target for modulating endocannabinoid and fatty acid ethanolamide signaling, which may have important therapeutic potential. We recently described a new class of O-arylcarbamate inhibitors of FAAH, including the cyclohexylcarbamic acid biphenyl-3-yl ester URB524 (half-maximal inhibitory concentration, IC50 = 63 nM), which have significant anxiolytic-like properties in rats. In the present study, by introducing a selected group of substituents at the meta and para positions of the distal phenyl ring of URB524, we have characterized structure-activity profiles for this series of compounds and shown that introduction of small polar groups in the meta position greatly improves inhibitory potency. Most potent in the series was the m-carbamoyl derivative URB597 (4i, IC50 = 4.6 nM). Furthermore, quantitative structure-activity relationship (QSAR) analysis of an extended set of meta-substituted derivatives revealed a negative correlation between potency and lipophilicity and suggested that small-sized substituents may undertake polar interactions with the binding pocket of the enzyme. Docking studies and molecular dynamics simulations, using the crystal structure of FAAH, indicated that the O-biphenyl scaffold of the carbamate inhibitors can be accommodated within a lipophilic region of the substrate-binding site, where their folded shape mimics the initial 10-12 carbon atoms of the arachidonyl moiety of anandamide (a natural FAAH substrate) and methyl arachidonyl fluorophosphonate (a nonselective FAAH inhibitor). Moreover, substituents at the meta position of the distal. phenyl ring can form hydrogen bonds with atoms located on the polar section of a narrow channel pointing toward the membrane-associated side of the enzyme. The structure-activity characterization reported here should help optimize the pharmacodynamic and pharmacokinetic properties of this class of compounds.