3-methoxy-[1,1';3',1'']terphenyl | 156941-81-0

• 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: 3-methoxy-[1,1';3',1'']terphenyl
• 英文别名: 3-Methoxy-1,1a(2):3a(2),1a(2)a(2)-terphenyl；1-methoxy-3-(3-phenylphenyl)benzene
• CAS: 156941-81-0
• 化学式: C₁₉H₁₆O
• 分子量: 260.335
• InChiKey: HGCYXYLFPTUVGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-methoxy-[1,1';3',1'']terphenyl 在 氢碘酸 作用下， 反应 2.0h， 以97%的产率得到[1,1';3',1'']terphenyl-3''-ol
  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-溴联苯 、 3-甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 3.0h， 以97%的产率得到3-methoxy-[1,1';3',1'']terphenyl
  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

• N,S-chelating triazole-thioether ligand for highly efficient palladium-catalyzed Suzuki reaction
  作者：Qiong Yan、Lei Zheng、Miaomiao Li、Yunfeng Chen

  DOI：10.1016/j.jcat.2019.07.004

  日期：2019.8

  1,2,3-Triazole-thioether compounds could serve as efficient ligands for Pd-catalyzed Suzuki reactions of various aryl iodides, bromides and chlorides. The reactions feature wide substrate scope and mild reaction conditions. Besides, shorter reaction time, lower catalyst loadings and quantitative yields with a turnover-frequency (TOF) value of up to 11,880 h−1 are other advantageous of this attractive

  1,2,3-三唑-硫醚化合物可以用作钯催化的各种芳基碘化物，溴化物和氯化物的Suzuki反应的有效配体。该反应具有广泛的底物范围和温和的反应条件。此外，更短的反应时间，更低的催化剂载量和定量产率（TOF）值高达11,880 h -1的定量收率是该引人注目的方案的其他优点。晶体结构分析和计算研究表明，相应的螯合钯配合物的较高催化活性归因于较低的能隙和较低的氧化还原电势。
• Gold-catalyzed synthesis of 1,3-disubstituted benzenes through tandem allylation/cyclization reaction of alkynals
  作者：Sabyasachi Bhunia、Shariar Md. Abu Sohel、Chao-Chin Yang、Shie-Fu Lush、Fwu-Ming Shen、Rai-Shung Liu

  DOI：10.1016/j.jorganchem.2008.10.049

  日期：2009.2

  Treatment of alkynals with 2-substituted allylsilanes and PPh3AuCl/AgOTf (5/3 mol%) catalyst led to formation of 1,3-disubstituted benzenes efficiently. This reaction sequence comprises an initial allylation of aldehyde, followed by cycloisomerization of enynes; PPh3AuOTf is active in both steps.

  用2-取代的烯丙基硅烷和PPh 3 AuCl / AgOTf（5/3 mol％）催化剂处理炔烃可有效地形成1,3-二取代的苯。该反应顺序包括醛的初始烯丙基化，然后是烯炔的环异构化。PPh 3 AuOTf在两个步骤中均处于活动状态。
• Reductive Coupling of Aryl Halides <i>via</i> C—H Activation of Indene
  作者：Bo‐Sheng Zhang、Ying‐Hui Yang、Fan Wang、Xue‐Ya Gou、Xi‐Cun Wang、Yong‐Min Liang、Yuke Li、Zheng‐Jun Quan

  DOI：10.1002/cjoc.202100034

  日期：2021.6

  the first case of a reductive coupling reaction with indene, a non-heteroatom olefin used as a reducing agent. The scope of the substrate is wide. The homo-coupling, cross-coupling, and synthesis of 12 and 14-membered rings were realized. The control experiment, indene-product curve and density functional theory calculations showed that the η3-palladium indene intermediate was formed by C—H activation

  本文介绍了与茚（一种用作还原剂的非杂原子烯烃）进行还原偶联反应的第一种情况。基板的范围很广。实现了12和14元环的均偶联，交叉偶联和合成。在对照实验中，茚产物曲线和密度泛函理论计算表明，η 3 -钯茚中间体通过C-H活化在碳酸铯的存在下形成的。我们推测最终产物是通过Pd（IV）中间体或芳基配体交换获得的。此外，我们排除了钯阴离子（Pd（0）-）中间体的形成。
• Modular Access to <i>meta</i>-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation
  作者：Yi-Zhe Yu、Jin Bai、Jia-Min Peng、Jia-Sheng Yao、Chun-Xiang Zhuo

  DOI：10.1021/jacs.3c01330

  日期：——

  The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming

  取代苯衍生物对有机合成、药物化学和材料科学至关重要。然而，1,3-二-和 1,3,5-三取代苯在小分子药物中的普遍性远低于其他取代模式，这可能是由于缺乏稳健、高效和方便的合成方法。在这里，我们报告了一种 Mo 催化的分子间脱氧苯形成反应，该反应是现成的炔酮和烯丙基胺的反应。通过使用市售的钼催化剂，以高达 88% 的收率获得了多种不对称和未官能化的 1,3-二和 1,3,5-三取代苯。通过生物活性分子的合成转化、放大合成和衍生化进一步说明了该方法的合成潜力。初步的机理研究表明，这种苯形成过程可能通过钼催化的氮杂迈克尔加成/[1,5]-氢化物转移/环化/芳构化级联进行。该策略不仅为各种间位取代的苯衍生物，但也证明了钼催化在具有挑战性的分子间脱氧交叉偶联反应中的潜力。
• 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.