2-苯基-4(5)-(3-硝基苯基)咪唑 | 119512-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-苯基-4(5)-(3-硝基苯基)咪唑
• 英文名称: 2-phenyl-4(5)-(3-nitrophenyl)imidazole
• 英文别名: 4-(3-nitrophenyl)-2-phenylimidazole；5-(3-nitrophenyl)-2-phenyl-1H-imidazole
• CAS: 119512-11-7
• 化学式: C₁₅H₁₁N₃O₂
• 分子量: 265.271
• InChiKey: UETFLPDACAHRSE-UHFFFAOYSA-N

物化性质

• 熔点：
  270-273 °C(Solvent: Ethanol ; Diethyl ether)
• 沸点：
  533.7±33.0 °C(Predicted)
• 密度：
  1.304±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基-4(5)-(3-硝基苯基)咪唑 在 sodium hydride 作用下， 以 溶剂黄146 为溶剂， 反应 10.0h， 生成 1-Methyl-4-[[3-methyl-5-(3-nitrophenyl)-2-phenylimidazol-4-yl]methyl]piperazine
  参考文献：
  名称：

  Studies on Cerebral Protective Agents. VII. Synthesis of Novel 4-Arylazole Derivatives with Anti-anoxic Activity.

  摘要：

  新型4元氮杂环（即噻唑、噁唑和咪唑）衍生物，其氮杂环第5位具有氨基基团，被制备并用于测试对小鼠的抗缺氧（AA）活性。其中，5-（4-甲基哌嗪-1-基）甲基-4-（3-硝基苯基）-2-苯基噻唑（3b，FR75094）显示出显著的AA活性（分别为10 mg/kg腹腔注射和100 mg/kg口服），并且在抗脂质过氧化（ALP）测试中有效，抑制了花生四烯酸引起的大鼠脑水肿。讨论了这一系列化合物在AA活性方面的构效关系。

  DOI：

  10.1248/cpb.43.947
• 作为产物：
  描述：

  间硝基苯乙酮 在 ammonium acetate 、 氢溴酸 、 二甲基亚砜 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 36.0h， 生成 2-苯基-4(5)-(3-硝基苯基)咪唑
  参考文献：
  名称：

  从酮和醛模块合成二取代和三取代的咪唑：激酶抑制剂的途径。

  摘要：

  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。

  DOI：

  10.1021/acs.joc.9b01844

文献信息

• Base-Mediated Syntheses of Di- and Trisubstituted Imidazoles from Amidine Hydrochlorides and Bromoacetylenes
  作者：Xiao Yun Chen、Ulli Englert、Carsten Bolm

  DOI：10.1002/chem.201502707

  日期：2015.9.14

  A new transition metal‐free method for the preparation of substituted imidazoles from easy‐to‐handle amidine hydrochlorides and bromoacetylenes has been developed. The reactions proceed in air and use inexpensive K2CO3 as base. Additions of 2,2′‐bipyridine and water have beneficial effects on the product yields. Various di‐ and trisubstituted imidazoles have been prepared in good yields (up to 88 %)

  已开发出一种新的无过渡金属的方法，该方法由易于处理的am盐酸盐和溴乙炔制备取代的咪唑。反应在空气中进行，并使用廉价的K 2 CO 3作为碱。添加2,2'-联吡啶和水对产品收率有有利影响。各种二，三取代的咪唑均以高收率（高达88％）制备。
• Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models
  作者：Valentina Zuliani、Marco Fantini、Aradhya Nigam、James P. Stables、Manoj K. Patel、Mirko Rivara

  DOI：10.1016/j.bmc.2010.09.029

  日期：2010.11.15

  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.
• A Practical Synthesis of 2,4(5)-Diarylimidazoles from Simple Building Blocks
  作者：Valentina Zuliani、Giuseppe Cocconcelli、Marco Fantini、Chiara Ghiron、Mirko Rivara

  DOI：10.1021/jo070187d

  日期：2007.6.1

  A simple and efficient approach to selectively obtain 2,4(5)-diarylimidazoles suppressing formation of 2-aroyl-4(5)-arylimidazoles is described. The yield of each of the two products strongly depends on the reaction conditions employed. This reaction provides a simple method to prepare small libraries of biologically active compounds by parallel synthesis.
• 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。
• Studies on Cerebral Protective Agents. VII. Synthesis of Novel 4-Arylazole Derivatives with Anti-anoxic Activity.
  作者：Mitsuru OHKUBO、Atsushi KUNO、Hiroyoshi SAKAI、Hisashi TAKASUGI

  DOI：10.1248/cpb.43.947

  日期：——

  Novel 4-arylazole (i.e. thiazole, oxazole, and imidazole) derivatives, possessing an amino moiety at the C-5 position of the azole ring, were prepared and tested for anti-anoxic (AA) activity in mice. Among them, 5-(4-methylpiperazin-1-yl)methyl-4-(3-nitrophenyl)-2-phenylthiazole (3b, FR75094) possessed significant AA activity (10 mg/kg, i.p. and 100 mg/kg, p.o., respectively), and was also effective on anti-lipid peroxidation (ALP) assay and inhibited arachidonate-induced cerebral edema in rats. Structure-activity relationships in regard to AA activity of this series of compounds are discussed.

  新型4元氮杂环（即噻唑、噁唑和咪唑）衍生物，其氮杂环第5位具有氨基基团，被制备并用于测试对小鼠的抗缺氧（AA）活性。其中，5-（4-甲基哌嗪-1-基）甲基-4-（3-硝基苯基）-2-苯基噻唑（3b，FR75094）显示出显著的AA活性（分别为10 mg/kg腹腔注射和100 mg/kg口服），并且在抗脂质过氧化（ALP）测试中有效，抑制了花生四烯酸引起的大鼠脑水肿。讨论了这一系列化合物在AA活性方面的构效关系。