5-amino-1-(4-fluorophenyl)-1H-imidazole-4-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-1-(4-fluorophenyl)-1H-imidazole-4-carbonitrile
• 英文别名: 5-Amino-1-(4-fluorophenyl)imidazole-4-carbonitrile
• 化学式: C₁₀H₇FN₄
• 分子量: 202.191
• InChiKey: DMSORLOFGLAYJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-1-(4-fluorophenyl)-1H-imidazole-4-carbonitrile 在 乙酸酐 、 sodium carbonate 作用下， 以 水 为溶剂， 生成 N-(4-cyano-1-(4-fluorophenyl)-1H-imidazol-5-yl)-2-imino-8-methoxy-2H-chromene-3-carboxamide
  参考文献：
  名称：

  New chromene scaffolds for adenosine A2A receptors: Synthesis, pharmacology and structure–activity relationships

  摘要：

  In silico screening of a c ollection of 1584 academic compounds identified a small molecule hit for the human adenosine A(2A) receptor (pK(i) = 6.2) containing a novel chromene scaffold (3a). To explore the structure activity relationships of this new chemical series for adenosine receptors, a focused library of 43 2H-chromene-3-carboxamide derivatives was synthesized and tested in radioligand binding assays at human adenosine A(1), A(2A), A(2B) and A(3) receptors. The series was found to be enriched with bioactive compounds for adenosine receptors, with 14 molecules showing submicromolar affinity (pK(i) >= 6.0) for at least one adenosine receptor subtype. These results provide evidence that the chromene scaffold, a core structure present in natural products from a wide variety of plants, vegetables, and fruits, constitutes a valuable source for novel therapeutic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.009
• 作为产物：
  描述：

  N'-(2-amino-1,2-dicyanovinyl)-N-(4-fluorophenyl)formimidamide 在 potassium hydroxide 作用下， 生成 5-amino-1-(4-fluorophenyl)-1H-imidazole-4-carbonitrile
  参考文献：
  名称：

  腺嘌呤衍生物：治疗乳腺癌的有希望的候选者

  摘要：

  我们感谢 Minho 大学、Fundacao para a Ciencia ea Tecnologia (FCT) 和 FEDER-COMPETE 通过 Centro de Quimica (UID/QUI/00686/2013 和 UID/QUI/0686/2016) 的财政支持。NMR 波谱仪 Bruker Avance III 400 是国家核磁共振网络 (RNRMN) 的一部分，是在国家科学再设备计划框架内购买的，合同 REDE/1517/RMN/2005，资金来自 POCI 2010 (FEDER) 和FCT。这项工作也是在 NORTE-01-0145-FEDER-000013 项目的范围内开发的，由葡萄牙伙伴关系协议下的北葡萄牙区域运营计划 (NORTE 2020) 通过欧洲区域发展基金 (FEDER) 提供支持，以及通过竞争力因素运营计划 (COMPETE) 和国家基金，通过

  DOI：

  10.1002/ejoc.201800629

文献信息

• Anticancer potential of some imidazole and fused imidazole derivatives: exploring the mechanism <i>via</i> epidermal growth factor receptor (EGFR) inhibition
  作者：Sourav Kalra、Gaurav Joshi、Manvendra Kumar、Sahil Arora、Harsimrat Kaur、Sandeep Singh、Anjana Munshi、Raj Kumar

  DOI：10.1039/d0md00146e

  日期：——

  Imidazole-based epidermal growth factor receptor (EGFR) inhibitors were computationally designed and synthesized. All the compounds were assessed for their anti-proliferative activity against five cancer cell lines, viz., MDA-MB-231 (breast), T47D (breast) and MCF-7 (breast), A549 (lung) and HT-29 (colorectal). Compounds 2c and 2d emerged as better anticancer molecules with no toxicity towards normal

  基于咪唑的表皮生长因子受体 (EGFR) 抑制剂是通过计算设计和合成的。评估了所有化合物对五种癌细胞系的抗增殖活性，即。、MDA-MB-231（乳房）、T47D（乳房）和 MCF-7（乳房）、A549（肺）和 HT-29（结肠直肠）。化合物2c和2d成为更好的抗癌分子，对正常细胞没有毒性。2c和2d在体外抑制EGFR酶活性，IC 50值分别为617.33 ± 0.04 nM和710 ± 0.05 nM。为了进一步提高效力，我们探索了EGFR的ATP结合域的一个未被占用的区域并对其进行了分析2c和2d -EGFR 配合物的计算机相互作用模型，该模型引导并允许在 N-9 位置用 4-(4-甲基哌嗪基)-3-硝基苯基取代 4-氟苯基环（2c和2d ），得到化合物3c具有更好的结合评分和有效的 EGFR 抑制活性 (IC 50 : 236.38 ± 0.04 nM)，与阳性对照厄洛替尼 (239.91
• Investigation into Sonogashira reaction on 5-iodo-1-(phenyl/<i>p</i>-halophenyl)imidazole-4-carbonitrile compounds
  作者：Aniruddha Das

  DOI：10.1080/00397911.2017.1373298

  日期：2017.12.2

  arbonitrile compounds had been developed by introducing an iodo atom at the C-5 position of the imidazole ring of 5-amino-1-(phenyl/p-halophenyl)imidazole-4-carbonitrile compounds. Specifically, 5-iodo-1-(4-iodophenyl)imidazole-4-carbonitrile compound had shown double Sonogashira coupling reactions with two differently substituted iodine along with the formation of two other compounds where an unusual

  摘要 通过在 5-氨基-1-咪唑环的 C-5 位引入碘原子，对 5-碘-1-(苯基/对-卤代苯基)咪唑-4-甲腈化合物的 Sonogashira 反应进行了研究。 (苯基/对卤苯基)咪唑-4-腈化合物。具体来说，5-iodo-1-(4-iodophenyl)imidazole-4-carbonitrile 化合物与两种不同取代的碘发生双重 Sonogashira 偶联反应，同时形成另外两种化合物，其中获得了一种不寻常的具有自聚集性质的偶联产物. 在其他情况下，观察到单偶联与另一种化合物一起出现，其中存在于咪唑 C5 位置的碘原子被氢原子取代。图形概要
• Synthesis, X-ray crystallographic studies, DFT calculations and nanostructural features of annulated imidazo[4,5-<i>b</i>]pyridine derivatives
  作者：Aniruddha Das

  DOI：10.1080/00397911.2017.1381882

  日期：2017.12.17

  5-b]pyridine. Single X-ray crystallographic diffraction studies had shown that compounds had different types of heterodimeric, homodimeric π–π stacking, T-type stacking, and intermolecular hydrogen bonds which lead to nanostructure formation detected by scanning electron microscope. DFT calculation had also been performed to quantify heterodimeric π–π and T-stacking interactions. GRAPHICAL ABSTRACT

  摘要 5-氨基-4-氰基-1-(苯基/对-取代苯基)咪唑与环烷酮的Friedländer型缩合是通过将混合物与无水氯化铝在干燥的1,2-二氯乙烷中的悬浮液回流以产生7-氨基-3-芳基(5,6)环烷基咪唑并[4,5-b]吡啶。单 X 射线晶体衍射研究表明，化合物具有不同类型的异二聚体、同二聚体 π-π 堆积、T 型堆积和分子间氢键，这导致扫描电子显微镜检测到纳米结构的形成。还进行了 DFT 计算以量化异二聚体 π-π 和 T 堆积相互作用。图形概要
• Synthesis and radical scavenging activity of phenol–imidazole conjugates
  作者：Carla Correia、Cláudia Leite、M. Fernanda Proença、M. Alice Carvalho

  DOI：10.1016/j.bmcl.2014.04.026

  日期：2014.6

  Novel hydroxylated benzylideneamino imidazole derivatives were synthesized and their radical scavenging activity was assessed against DPPH and hydroxyl radicals. In the DPPH assay, most of the synthesized compounds showed an IC50 in the range 3.2 mu M <= IC50 <= 8.4 mu M, lower than the reference compound trolox (IC50 = 9.5 mu M) or the parent aldehydes (5.4 mu M <= IC50 <= 11.6 mu M). The activity depends mainly on the phenolic subunit (number and position of the hydroxyl groups) and the extent of conjugation with the imidazole ring. In the deoxyribose assay, all the compounds, including parent imidazoles and aldehydes, showed high activity against the hydroxyl radical and the ability to chelate iron ions. At 5 mu M concentration, the compounds protected the deoxyribose from degradation by hydroxyl radical between 62% and 38%. (C) 2014 Elsevier Ltd. All rights reserved.
• Studies on complex π-π and T-stacking features of imidazole and phenyl/p-halophenyl units in series of 5-amino-1-(phenyl/p-halophenyl)imidazole-4-carboxamides and their carbonitrile derivatives: Role of halogens in tuning of conformation
  作者：Aniruddha Das

  DOI：10.1016/j.molstruc.2017.06.124

  日期：2017.11

  5-amino-1-(phenyl/p-halophenyl)imidazole-4-carboxamides (N-phenyl AICA) (2a-e) and 5-amino-1-(phenyl/p-halophenyl)imidazole-4-carbonitriles (N-phenyl AICN) (3a-e) had been synthesized. X-ray crystallographic studies of 2a-e and 3a-e had been performed to identify any distinct change in stacking patterns in their crystal lattice. Single crystal X-ray diffraction studies of 2a-e revealed pi-pi stack formations with both imidazole and phenyl/p-halophenyl units in anti and syn parallel-displaced (PD)-type dispositions. No pi-pi stacking of imidazole occurred when the halogen substituent is bromo or iodo; pi-pi stacking in these cases occurred involving phenyl rings only. The presence of an additional T-stacking had been observed in crystal lattices of 3a-e. Vertical pi-pi stacking distances in anti-parallel PD-type arrangements as well as T-stacking distances had shown stacking distances short enough to impart stabilization whereas syn-parallel stacking arrangements had got much larger pi-pi stacking distances to belie any syn-parallel stacking stabilization. DFT studies had been pursued for quantifying the pi-pi stacking and T-stacking stabilization. The plotted curves for anti-parallel and T-stacked moieties had similarities to the 'Morse potential energy curve for diatomic molecule'. The minima of the curves corresponded to the most stable stacking distances and related energy values indicated stacking stabilization. Similar DFT studies on syn-parallel systems of 2b corresponded to no pi-pi stacking stabilization at all. Halogen-halogen interactions had also been observed to stabilize the compounds 2d, 2e and 3d. Nano-structural behaviour of the series of compounds 2a-e and 3a-e were thoroughly investigated. (C) 2017 Elsevier B.V. All rights reserved.