2-(4,5-di-p-tolyl-1H-imidazol-2-yl)phenol | 169155-32-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-(4,5-di-p-tolyl-1H-imidazol-2-yl)phenol
• 英文别名: Phenol, 2-[4,5-bis(4-methylphenyl)-1H-imidazol-2-yl]-；2-[4,5-bis(4-methylphenyl)-1H-imidazol-2-yl]phenol
• CAS: 169155-32-2
• 化学式: C₂₃H₂₀N₂O
• 分子量: 340.425
• InChiKey: TWZXERQCYYRPEF-UHFFFAOYSA-N

物化性质

• 熔点：
  223 °C
• 沸点：
  557.8±38.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  48.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  邻甲基苄醇 、 4,4'-二甲基联苯甲酰 在 乙酸铵 、 1-butylimidazolium tetrafluoroborate 作用下， 反应 1.17h， 以90%的产率得到2-(4,5-di-p-tolyl-1H-imidazol-2-yl)phenol
  参考文献：
  名称：

  室温离子液体促进了由芳基醛和1,2-二酮或α-羟基酮快速合成2,4,5-三芳基咪唑

  摘要：

  描述了一种在室温离子液体中改进，快速的一锅法合成2,4,5-三芳基咪唑，不需要任何添加的催化剂。筛选了基于1-正丁基和1,3-二正丁基咪唑鎓盐的不同离子液体，其在酸度和极性方面的功效与产率和反应时间相关。一锅法可在较短的反应时间内获得出色的分离收率，其特点是后处理步骤简单，可有效回收和循环用作助催化剂的离子液体。

  DOI：

  10.1016/j.tet.2005.01.116

文献信息

• Design, Synthesis and Evaluation of Unique 2,4,5-triaryl Imidazole Derivatives as Novel Potent Aspartic Protease Inhibitors
  作者：Mohd Sajid Khan、Salman Akhtar、S. A. Siddiqui、M. S. Siddiqui、K. V. Srinivasan、J. M. Arif

  DOI：10.2174/1573406411208030428

  日期：2012.5.1

  The 2,4,5-triaryl imidazole derivatives (API) were designed, screened and characterized kinetically & thermodynamically against Pepsin and their activity was also tested on the in silico platform. The docking studies of API with Pepsin show that these are novel and unique inhibitors of Aspartic protease. Drug like properties of these compounds were validated in silico based on Lipinski's rule of Five by calculating ClogP, LogS, H-bond acceptors, H-Bond donors, rotational bonds, PSA, PB and BBB values. The Et/Ki and Et/Km values of API show that they follow the Michaelis-Menten kinetics. The binding of inhibitors with proteases was explained by using Van't Hoff plot and thermodynamic parameters viz. free energy (ΔG), Entropy (ΔS) and Enthalpy (ΔH). The Van't Hoff analysis showed that the value of Ki decreases with increase in temperature and the binding of the inhibitor are entropically driven. API act as new potent aspartic protease inhibitors with Ki, for Pepsin, ranges from 3.7 µM to 16.7 µM. Strong hydrophobic groups at C-4 & C-5 position in API favor binding of inhibitors with Pepsin. Experiments also showed that among C-2 aryl substituted imidazole, a 4-substitution on aryl ring is preferred and less polar substituent makes the molecule more active whereas polar substituents at 2-position on C-2 aryl ring makes the molecule less active. The docking studies of API with Pepsin further intensify and validate our results.

  2,4,5-三芳基咪唑衍生物（API）被设计、筛选并在动力学和热力学方面鉴定，与胃蛋白酶进行对比，其活性也在计算机模拟平台上进行了测试。API与胃蛋白酶的对接研究表明，这些化合物是天冬氨酸蛋白酶的新型独特抑制剂。这些化合物的药物样性质通过计算ClogP、LogS、氢键受体、氢键供体、旋转键、极性表面积（PSA）、分配系数（PB）和血脑屏障（BBB）值，依据Lipinski五规则进行了计算验证。API的Et/Ki和Et/Km值表明它们遵循迈克利斯-门腾动力学。抑制剂与蛋白酶的结合通过范特霍夫图和热力学参数（即自由能（ΔG）、熵（ΔS）和焓（ΔH））进行了阐释。范特霍夫分析显示，Ki值随着温度的升高而降低，抑制剂的结合是由熵驱动的。API作为新的有效天冬氨酸蛋白酶抑制剂，对于胃蛋白酶，其Ki值范围为3.7 µM至16.7 µM。API在C-4和C-5位的强疏水基团有利于抑制剂与胃蛋白酶的结合。实验还表明，C-2芳基取代的咪唑中，4位取代的芳基环更受欢迎，且较不极性的取代基使分子活性增强，而C-2芳基环2位的极性取代基会使分子活性降低。API与胃蛋白酶的对接研究进一步加强并验证了我们的结果。
• Room temperature ionic liquid promoted improved and rapid synthesis of 2,4,5-triaryl imidazoles from aryl aldehydes and 1,2-diketones or α-hydroxyketone
  作者：Shapi A. Siddiqui、Umesh C. Narkhede、Sanjay S. Palimkar、Thomas Daniel、Rajgopal J. Lahoti、Kumar V. Srinivasan

  DOI：10.1016/j.tet.2005.01.116

  日期：2005.4

  An improved and rapid one-pot synthesis of 2,4,5-triaryl imidazoles in a room temperature ionic liquid is described, which does not need any added catalyst. Different ionic liquids based on 1-n-butyl and 1,3-di-n-butyl imidazolium salts were screened and their efficacy in terms of acidity and polarity have been correlated with yields and reaction period. The one-pot methodology resulting in excellent

  描述了一种在室温离子液体中改进，快速的一锅法合成2,4,5-三芳基咪唑，不需要任何添加的催化剂。筛选了基于1-正丁基和1,3-二正丁基咪唑鎓盐的不同离子液体，其在酸度和极性方面的功效与产率和反应时间相关。一锅法可在较短的反应时间内获得出色的分离收率，其特点是后处理步骤简单，可有效回收和循环用作助催化剂的离子液体。