2-(4-methoxyphenyl)-5-(4-methoxyphenyl)-1H-imidazole | 97978-70-6

• 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)-5-(4-methoxyphenyl)-1H-imidazole
• 英文别名: 2,5-bis(4-methoxyphenyl)-1H-imidazole
• CAS: 97978-70-6
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: ZHXXCWMUBSJFQU-UHFFFAOYSA-N

物化性质

• 沸点：
  517.6±40.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methoxyphenyl)-5-(4-methoxyphenyl)-1H-imidazole 在 boron trifluoride dimethyl sulfide complex 作用下， 以 二氯甲烷 为溶剂， 反应 20.0h， 以17%的产率得到4,4'-(1H-imidazol-2,5-diyl)diphenol
  参考文献：
  名称：

  设计，合成和生物学评估作为有效和选择性的非甾体抑制剂17beta-羟类固醇脱氢酶1型（17beta-HSD1）的双（羟苯基）唑类药物，用于治疗雌激素依赖性疾病。

  摘要：

  17beta-羟基类固醇脱氢酶1（17beta-HSD1）催化将活性较弱的雌酮（E1）还原为最有效的雌激素17beta-雌二醇（E2）。E2通过激活雌激素受体（ER）刺激激素依赖性疾病的生长。17beta-HSD1通常在乳腺癌细胞中过表达。因此，它是治疗乳腺肿瘤的有吸引力的靶标。配体和基于结构的药物设计方法的结合导致了对双（羟苯基）唑类化合物作为17β-HSD1潜在抑制剂的鉴定。研究了不同的唑和羟基取代方式。评估了化合物相对于17beta-HSD2，ERalpha和ERbeta的活性和选择性。最有效的化合物是3- [5-（4-羟基苯基）-1,3-恶唑-2-基]苯酚（18，IC（50）= 0.31 microM），

  DOI：

  10.1016/j.bmc.2008.04.073
• 作为产物：
  描述：

  2-氨基-1-(4-甲氧苯基)-苯乙酮盐酸盐 在 ammonium acetate 、 三乙胺 作用下， 以 乙醚 、 溶剂黄146 为溶剂， 反应 20.0h， 生成 2-(4-methoxyphenyl)-5-(4-methoxyphenyl)-1H-imidazole
  参考文献：
  名称：

  17BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS FOR THE TREATMENT OF HORMONE-RELATED DISEASES

  摘要：

  该发明涉及17beta-羟基类固醇脱氢酶1型（17betaHSD1）抑制剂，其制备以及用于治疗和预防激素相关疾病，特别是雌激素相关或雄激素相关疾病的用途。

  公开号：

  US20110046147A1

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。
• [EN] BENZYLHYDROXYDE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF<br/>[FR] DÉRIVÉS DE BENZYLHYDROXYDE, LEUR PRÉPARATION ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：SANOFI SA

  公开号：WO2016066742A1

  公开（公告）日：2016-05-06

  The invention relates to benzylhydroxyde derivatives of formula (I): The invention also relates to the preparation and the therapeutic use of the compounds of formula (I).

  该发明涉及式(I)的苄基羟基衍生物。该发明还涉及式(I)化合物的制备和治疗用途。
• Thiadiazolium ylides: Substituted 2H-1,3,5-thiadiazines and 1,4,5-trisubstituted-imidazoles from 1,2,4- and 1,2,5-thiadiazolium-2-unsubstituted methanide (ylide) systems: ring expansions and ring interconversions via sulfur-nitrogen heterotriene intermediates. Mechanistic ab initio calculations. Azolium 1,3-dipoles
  作者：Richard N. Butler、Martin O. Cloonan、John M. McMahon、Luke A. Burke

  DOI：10.1039/a901148j

  日期：——

  Quaternisation of 3,5-diaryl-1,2,4-thiadiazoles with trimethylsilylmethyl triflate at 40 °C occurred at N-2. Separate desilylation of the salts resulted in a ring expansion to substituted 2H-1,3,5-thiadiazines 5. Heating of these with ethanolic sodium ethoxide caused sulfur extrusion and ring contraction to 2,4-disubstituted imidazoles 6. 3,4-Diaryl-1,2,5-thiadiazoles were less reactive to alkylation and trimethylsilylmethylation required heating at 80 °C. Treatment of the salts with CsF unexpectedly gave 1-trimethylsilylmethyl-4,5-diarylimidazoles 21. 1H, 13C, 15N NMR spectra are described and the mechanisms were studied by ab inito calculations with the GAUSSIAN94 series of programmes using the HF/6-31G* theoretical level.

  3,5-二芳基-1,2,4-噻二唑在40°C下与三甲基硅基甲基三氟甲磺酸酯的季铵化反应发生在N-2位。分离的盐的脱硅基化导致环的扩展，生成了取代的2H-1,3,5-噻二唑啉5。将这些化合物与醇钠乙氧基加热，会导致硫原子的排出和环的收缩，生成2,4-二取代的咪唑6。3,4-二芳基-1,2,5-噻二唑对烷基化反应的活性较低，三甲基硅基甲基化反应需要在80°C下加热。用CsF处理盐意外地生成了1-三甲基硅基甲基-4,5-二芳基咪唑21。描述了其1H、13C、15N NMR谱，并通过使用HF/6-31G*理论水平的GAUSSIAN94系列程序进行了机制研究。
• Design, synthesis and biological evaluation of bis(hydroxyphenyl) azoles as potent and selective non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) for the treatment of estrogen-dependent diseases
  作者：Emmanuel Bey、Sandrine Marchais-Oberwinkler、Patricia Kruchten、Martin Frotscher、Ruth Werth、Alexander Oster、Oztekin Algül、Alexander Neugebauer、Rolf W. Hartmann

  DOI：10.1016/j.bmc.2008.04.073

  日期：2008.6

  The combination of a ligand- and a structure-based drug design approach led to the identification of bis(hydroxyphenyl) azoles as potential inhibitors of 17beta-HSD1. Different azoles and hydroxy substitution patterns were investigated. The compounds were evaluated for activity and selectivity with regard to 17beta-HSD2, ERalpha and ERbeta. The most potent compound is 3-[5-(4-hydroxyphenyl)-1,3-oxazol-2-yl]phenol

  17beta-羟基类固醇脱氢酶1（17beta-HSD1）催化将活性较弱的雌酮（E1）还原为最有效的雌激素17beta-雌二醇（E2）。E2通过激活雌激素受体（ER）刺激激素依赖性疾病的生长。17beta-HSD1通常在乳腺癌细胞中过表达。因此，它是治疗乳腺肿瘤的有吸引力的靶标。配体和基于结构的药物设计方法的结合导致了对双（羟苯基）唑类化合物作为17β-HSD1潜在抑制剂的鉴定。研究了不同的唑和羟基取代方式。评估了化合物相对于17beta-HSD2，ERalpha和ERbeta的活性和选择性。最有效的化合物是3- [5-（4-羟基苯基）-1,3-恶唑-2-基]苯酚（18，IC（50）= 0.31 microM），
• Design and Synthesis of Tri-substituted Imidazole Derivatives as CD73 Inhibitors for Their Anticancer Activity
  作者：Abhishek Ghara、Ganesh Sakharam Andhale、Gurubasavaraja Swamy Purawarga Matada、Prasad Sanjay Dhiwar

  DOI：10.2174/1570180818666210604113849

  日期：2022.3

  Monoclonal antibodies licensed by the US Food and Drug Administration (FDA) target diverse biological targets relevant to immuno-oncology, and small compounds in clinical trials target various aspects of immuno-oncology. Several small compounds that target CD73 are at various stages of clinical studies. Several imidazoles are currently being utilized to treat malignancies, including Dacarbazine, Zoledronic acid, Mercaptopurine, and others. As a result, we evaluated the cytotoxicity of modified tri-phenyl imidazoles against breast cancer cell lines, as well as conducted virtual tests.

  We used Accelrys Drug Discovery Studio 3.5 software to undertake molecular docking, ADMET, and molecular properties studies on 68 proposed imidazole derivatives. The synthesized compounds' binding mechanisms were investigated against the CD73 protein (PDB Code: 4H1S). To find the drugs with the best pharmacokinetics, researchers assessed ADMET solubility, BBB penetration, hepatotoxicity, PPB binding, and polar surface area. The MDA-MB-231 breast cancer cell line was treated with these produced compounds, and the MTT test method was used to determine the IC50 values.

  The selected 14 compounds showed good binding in the active site of CD73 by forming Hbonds with amino acid residues, according to molecular docking studies. Breast cancer cell lines were treated with substituted tri-phenyl imidazole derivatives, which displayed anticancer activity. Compounds 3a and 3h, which had an electron-donating group at the 2nd and 3rd positions and p-substitutions of the chloro and nitro groups, respectively, showed considerable anticancer action.

  Fourteen imidazole derivatives were produced and tested against breast cancer cell lines based on in-silico research. The MDA-MB-231 cell line was strongly suppressed by compounds 3a and 3h. In-vitro enzyme inhibition experiments revealed that only 3h demonstrated considerable inhibition.

  背景：美国食品和药物管理局（FDA）批准的单克隆抗体针对免疫肿瘤学相关的多种生物靶点，临床试验中的小分子化合物则针对免疫肿瘤学的各个方面。目前有多种针对CD73的小分子化合物正在进行临床研究，包括达卡巴嗪、左氧氟沙宁、巯基嘌呤等。因此，我们评估了改性三苯基咪唑对乳腺癌细胞系的细胞毒性，并进行了虚拟测试。 方法：我们使用Accelrys Drug Discovery Studio 3.5软件对68种提出的咪唑衍生物进行了分子对接、ADMET和分子性质研究。研究人员对合成化合物的结合机制进行了CD73蛋白（PDB代码：4H1S）研究。为了找到具有最佳药代动力学的药物，研究人员评估了ADMET溶解度、BBB穿透性、肝毒性、PPB结合和极性表面积。这些合成化合物被用于治疗MDA-MB-231乳腺癌细胞系，并使用MTT测试方法确定了IC50值。 结果：根据分子对接研究，选择的14种化合物在CD73的活性位点上通过与氨基酸残基形成氢键表现出良好的结合。用取代三苯基咪唑衍生物处理乳腺癌细胞系，显示出抗癌活性。具有电子给体基团在第2和第3位置以及氯和硝基的p-取代的3a和3h化合物表现出了相当大的抗癌作用。 结论：基于体外研究，生产了14种咪唑衍生物并对其针对乳腺癌细胞系进行了测试。MDA-MB-231细胞系被3a和3h化合物强烈抑制。体外酶抑制实验表明，只有3h表现出了相当大的抑制作用。