1-[3-(3-羟基苯基)苯基]乙酮 | 365427-02-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-[3-(3-羟基苯基)苯基]乙酮
• 英文名称: 1-(3'-hydroxy-[1,1'-biphenyl]-3-yl)ethanone
• 英文别名: 1-(3'-hydroxybiphenyl-3-yl)ethanone；3-(3-Acetylphenyl)phenol；1-[3-(3-hydroxyphenyl)phenyl]ethanone
• CAS: 365427-02-7
• 化学式: C₁₄H₁₂O₂
• 分子量: 212.248
• InChiKey: AWTYPSRVOKBQPL-UHFFFAOYSA-N

物化性质

• 沸点：
  418.6±38.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  环己基异氰酸酯 、 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 8.0h， 以72%的产率得到Cyclohexyl-carbamic acid 3''''-acetyl-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-碘苯乙酮 、 水杨酸 在 [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl) palladium(II) dichloride 、 potassium carbonate 、 silver carbonate 作用下， 以 溶剂黄146 为溶剂， 反应 16.0h， 以77%的产率得到1-[3-(3-羟基苯基)苯基]乙酮
  参考文献：
  名称：

  Salicylic acids as readily available starting materials for the synthesis of meta-substituted biaryls

  摘要：

  水杨酸被证明是易得且多功能的起始物质，可以在钯催化下轻松地经历串联芳基化-质子脱羧过程。随后，相应的间位芳基酚可以轻松转化为各种间位功能化的联芳烃，突显了这种方法进入这种结构基元的多功能性。

  DOI：

  10.1039/c4cc09674f

文献信息

• Construction of a Polyheterocyclic Benzopyran Library with Diverse Core Skeletons through Diversity-Oriented Synthesis Pathway
  作者：Sangmi Oh、Hwan Jong Jang、Sung Kon Ko、Yeonjin Ko、Seung Bum Park

  DOI：10.1021/cc100044w

  日期：2010.7.12

  In this study, a divergent and practical solid-phase parallel diversity-oriented synthesis (DOS) strategy was successfully applied for the construction of five discrete core skeletons embedded with privileged benzopyranyl substructure. The diversity of these core skeletons was expanded through the introduction of various substituents at the R, R(1), and R(2) positions from a single key intermediate

  在这项研究中，发散和实用的固相平行分集定向合成（DOS）策略已成功地应用于构建五个嵌入有特权苯并吡喃基亚结构的离散核骨架。这些核心骨架的多样性通过在五个不同途径中的单个关键中间体在R，R（1）和R（2）位置处引入各种取代基而得到扩展。更重要的是，我们通过使用库到库的概念，通过核心骨架本身的转换来有效地最大化了分子多样性，并创建了具有相同构件的独特小分子集合。构建了一个434个成员的多杂环苯并吡喃文库，规模约为10 mg，具有进一步多样化的潜力。无需进一步纯化，
• [EN] SUBSTITUTED PARA-BIPHENYLOXYMETHYL DIHYDRO OXAZOLOPYRIMIDINONES, PREPARATION AND USE THEREOF<br/>[FR] PARA-BIPHÉNYLOXYMÉTHYL-DIHYDRO-OXAZOLOPYRIMIDINONES SUBSTITUÉES, LEUR PRÉPARATION ET LEUR UTILISATION
  申请人：SANOFI AVENTIS

  公开号：WO2011034828A1

  公开（公告）日：2011-03-24

  The present invention relates to a series of substituted para-biphenyloxymethyl dihydro oxazolopyrimidinones of formula (I) as defined herein. This invention also relates to methods of making these compounds including novel intermediates. The compounds of this invention are modulators of metabotropic glutamate receptors (mGluR), particularly, mGluR2 receptor. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic neurodegenerative conditions, psychoses, cognition deficit disorders, convulsions, anxiety, depression, migraine, pain, sleep disorders and emesis.

  本发明涉及一系列以本文所定义的式(I)的取代对联苯氧甲基二氢噁唑吡咯嘧啶酮。本发明还涉及制备这些化合物的方法，包括新颖的中间体。本发明的化合物是代谢型谷氨酸受体（mGluR），特别是mGluR2受体的调节剂。因此，本发明的化合物在药物代理方面是有用的，特别是在治疗和/或预防各种中枢神经系统疾病（CNS），包括但不限于急性和慢性神经退行性疾病、精神病、认知缺陷症、癫痫、焦虑、抑郁、偏头痛、疼痛、睡眠障碍和呕吐等方面。
• Overriding Ortho–Para Selectivity via a Traceless Directing Group Relay Strategy: The Meta-Selective Arylation of Phenols
  作者：Junfei Luo、Sara Preciado、Igor Larrosa

  DOI：10.1021/ja500457s

  日期：2014.3.19

  based on a traceless directing group relay strategy. In this process carbon dioxide is used as a transient directing group which facilitates a palladium catalyzed arylation meta to the phenol hydroxyl group with iodoarenes. This transformation proceeds with complete meta-selectivity and is compatible with a variety of functional groups both in the phenol and in the iodoarene coupling partner.

  酚在邻位和对位的直接官能化通常由羟基的给电子性质促进。另一方面，从母体酚中获取间位官能化酚通常需要冗长的合成序列。在这里，我们报告了苯酚的一锅直接间选择性芳基化的第一种方法。该方法基于无痕定向组中继策略。在该方法中，二氧化碳用作瞬时导向基团，其促进钯催化的芳基化与碘芳烃的苯酚羟基间位。这种转化以完全的间位选择性进行，并且与苯酚和碘芳烃偶联伙伴中的各种官能团相容。
• [EN] ENOL CARBAMATE DERIVATIVES AS MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] DÉRIVÉS CARBAMATES D'ÉNOL EN TANT QUE MODULATEURS DE L'HYDROLASE D'AMIDES D'ACIDES GRAS
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2009109504A1

  公开（公告）日：2009-09-11

  The invention provides novel enol carbamate derivatives of formula (I) for inhibiting Fatty Acid Amide Hydrolase (FAAH), compositions that include such compounds as well as methods of treating diseases of energy metabolism, central nervous system disorders, cardiovascular and respiratory disorders, retinopathy, cancer, gastrointestinal and liver disorders and/or musculoskeletal disorders. The compounds of the present invention proved particularly efficacious in animal models of anxiety and pain.

  该发明提供了一种用于抑制脂肪酸酰胺水解酶（FAAH）的新型烯醇氨基甲酸酯衍生物的化学式（I），包括这些化合物的组合物以及治疗能量代谢疾病、中枢神经系统疾病、心血管和呼吸系统疾病、视网膜病变、癌症、胃肠道和肝脏疾病和/或肌肉骨骼疾病的方法。本发明的化合物在动物模型中表现出特别有效的抗焦虑和止痛作用。
• 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.