2-(4-methoxyphenyl)-4-phenyl-1H-imidazole | 25206-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-methoxyphenyl)-4-phenyl-1H-imidazole
• 英文别名: 2-(4-methoxyphenyl)-5-phenyl-1H-imidazole
• CAS: 25206-04-6
• 化学式: C₁₆H₁₄N₂O
• 分子量: 250.3
• InChiKey: BUWHNKZFUTUGJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-4-phenyl-1H-imidazole 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 生成 2-(4-methoxyphenyl)-4(5)-phenylimidazole hydrochloride
  参考文献：
  名称：

  Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models

  摘要：

  2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNaV1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED(50)). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED(50) = 61.7 mg/kg; compound 13, ED(50) = 46.8 mg/kg, compound 17, ED(50) = 129.5 mg/kg and compound 20, ED(50) = 136.7 mg/kg). Protective indexes (PI = TD(50)/ED(50)) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNaV1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.029
• 作为产物：
  描述：

  4-phenyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)-1H-1,2,3-triazole 在 四(三苯基膦)钯 、 bis{rhodium[3,3'-(1,3-phenylene)bis(2,2-dimethylpropanoic acid)]} 、 sodium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 苯 为溶剂， 反应 21.0h， 生成 2-(4-methoxyphenyl)-4-phenyl-1H-imidazole
  参考文献：
  名称：

  Synthesis of 2-Bromoimidazoles from Alkynes, N-Sulfonylazides, and Bromocyanides

  摘要：

  A synthetic method for Z-bromoimidazoles is developed from Rh-catalyzed cyclization of N-sulfonyl-1,2,3-triazoles with bromocyanides. Cu-catalyzed [3 + 2] cycloaddition followed by Rh-catalyzed cyclization starting from alkynes, N-sulfonylazides, and bromocyanides is also demonstrated for de novo synthesis of 2-bromoimidazoles in one pot. Moreover, this work was successfully employed to introduce diverse functional groups to the 2-position of imidazoles via cross-coupling reaction.

  DOI：

  10.1021/acs.orglett.5b00977

文献信息

• Modular Synthesis of Di- and Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors
  作者：Ian de Toledo、Thiago A. Grigolo、James M. Bennett、Jonathan M. Elkins、Ronaldo A. Pilli

  DOI：10.1021/acs.joc.9b01844

  日期：2019.11.1

  A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol

  基于酮氧化，采用催化HBr和DMSO，然后通过咪唑与醛的缩合反应，开发了一种单罐模块化方法，用于合成2,4（5）-二取代的咪唑。该方法提供了二十九个二取代的NH-咪唑（23％-85％的产率）。通过采用这种氧化-缩合方案，然后在咪唑环中进行溴化和Suzuki偶联，得到三取代的NH-咪唑（23％-69％，三步法），实现了三步合成20种激酶抑制剂的过程。该方法还用于合成已知抑制剂GSK3037619A。
• Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides
  作者：Fabio Bellina、Chiara Calandri、Silvia Cauteruccio、Renzo Rossi

  DOI：10.1016/j.tet.2006.12.068

  日期：2007.2

  -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol

  在无配体和无碱条件下，各种π电子足够的杂芳烃（包括游离的（NH）-咪唑，-苯并咪唑和-吲哚）与Pd和Cu介导的反应与芳基碘化物在区域上选择性地提供了所需的2-高产率的芳基杂环衍生物。2-芳基-1-苯基-1 H-咪唑也可以通过在碱性条件下通过一锅多米诺骨牌HALEX以及Pd和Cu介导的1-苯基-1 H-咪唑与活化和未活化的芳基溴化物的芳基化反应来制备自由和无配体的条件。已经发现涉及使用芳基碘化物的2-芳基唑的合成方案适用于有效制备三种生物活性化合物和乙酰肝素酶抑制剂合成中的关键中间体。
• [EN] COMPOSITIONS AND METHODS FOR BLOCKING SODIUM CHANNELS<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE BLOCAGE DE CANAUX SODIQUES
  申请人：PATEL MANOJ K

  公开号：WO2018140504A1

  公开（公告）日：2018-08-02

  The disclosure provides methods for treating a subject suffering from a disease associated with sodium channel activity. The method comprises administering to the subject a therapeutically effective amount of a compound according to Formula II or Formula III described in the specification, or a pharmaceutically acceptable salt, prodrug, tautomer, stereoisomer, hydrate, or solvate thereof.

  该披露提供了治疗患有与钠通道活性相关的疾病的方法。该方法包括向受试者施用规范中描述的Formula II或Formula III中的化合物的治疗有效量，或其药用可接受的盐、前药、互变异构体、立体异构体、水合物或溶剂化合物。
• Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole
  作者：Fabio Bellina、Silvia Cauteruccio、Annarita Di Fiore、Chiara Marchetti、Renzo Rossi

  DOI：10.1016/j.tet.2008.01.051

  日期：2008.6

  direct C-2 arylation of imidazoles 9 with aryl halides under base-free and ligandless conditions. On the other hand, the four-step synthesis of imidazoles 1 from 8 also involves the regioselective bromination of compounds 9 and a Suzuki reaction of the resulting 5-aryl-1-benzyl-4-bromo-1H-imidazoles 11 with arylboronic acids 5 under phase-transfer conditions, followed by N-debenzylation.

  为4（5）的制备高度选择性的，实用，高效的协议-芳基- 1 H ^ -咪唑2，2,4（5）-diaryl-1 ħ -咪唑3，和4,5-二芳基-1- ħ -描述了咪唑1。这些协议的关键步骤是通过Pd催化商用C 1-苄基1 H-咪唑（8）与芳基卤化物的直接C-5芳基化反应，选择性合成5-芳基-1-苄基1 H-咪唑9-区域选择性。。由8的化合物3的三步合成还涉及咪唑的Pd催化和Cu介导的直接C-2芳基化反应9在无碱和无配体条件下与芳基卤化物反应。另一方面，由8的四步合成咪唑1还涉及化合物9的区域选择性溴化和所得的5-芳基-1-苄基-4-溴-1 H-咪唑11与芳基硼酸的Suzuki反应。在相转移条件下为5，然后进行N-脱苄基作用。
• Efficient and Practical Synthesis of 4(5)-Aryl-1<i>H</i>-imidazoles and 2,4(5)-Diaryl-1<i>H</i>-imidazoles via Highly Selective Palladium-Catalyzed Arylation Reactions
  作者：Fabio Bellina、Silvia Cauteruccio、Renzo Rossi

  DOI：10.1021/jo701496p

  日期：2007.10.1

  be efficiently and selectively prepared by PdCl2(dppf)-catalyzed Suzuki−Miyaura reaction of commercially available 4(5)-bromo-1H-imidazole with arylboronic acids under phase-transfer conditions. On the other hand, N-unprotected 4(5)-aryl-1H-imidazoles can undergo highly selective Pd(OAc)2-catalyzed and CuI-mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and

  通过PdCl 2（dppf）催化的Suzuki-Miyaura反应可在相转移条件下对市售4（5）-bromo-1 H-咪唑与芳基硼酸进行反应，可有效地选择性制备4（5）-Aryl-1 H-咪唑条件。另一方面，N-未保护的4（5）-芳基-1 H-咪唑可在碱下与多种芳基溴化物和碘化物进行高选择性Pd（OAc）2催化和CuI介导的直接C-2-芳基化无和无配体的条件下，以适度到良好的产率生产2,4（5）-二芳基-1 H-咪唑。在用于制备2,4（5）-二芳基-1 H-咪唑的实验条件下未观察到N-芳基化副产物。