2-phenyl-N-(p-tolyl)-quinoline-4-carboxamide | 88067-76-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-phenyl-N-(p-tolyl)-quinoline-4-carboxamide
• 英文别名: N-(4-methylphenyl)-2-phenylquinoline-4-carboxamide
• CAS: 88067-76-9
• 化学式: C₂₃H₁₈N₂O
• 分子量: 338.409
• InChiKey: PMSHRZMEDDFETM-UHFFFAOYSA-N

物化性质

• 沸点：
  482.5±45.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-苯基-4-喹啉羧酸 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-phenyl-N-(p-tolyl)-quinoline-4-carboxamide
  参考文献：
  名称：

  Small Molecule Quantification by Liquid Chromatography-Mass Spectrometry for Metabolites of Drugs and Drug Candidates

  摘要：

  药物及药物候选物代谢物的鉴定和定量通常使用液相色谱-质谱联用技术 (LC-MS) 进行。最佳实践是生成以代谢物与内标的标准曲线。然而，为了避免代谢物合成的困难，有时会使用底物来准备标准曲线，假设底物和代谢物的信号是等效的。我们使用一系列非常相似的化合物，这些化合物经历共同的代谢反应，测试了这一假设所带来的误差，采用了传统流动电喷雾电离 LC-MS 和低流量捕获喷雾电离 (CSI) LC-MS 方法。文中展示了四种不同转化类型（O-去甲基化、N-去甲基化、芳香族羟基化和苄基羟基化）的标准曲线差异。结果表明，在20种底物-代谢物组合中的18种情况下，两种方法中底物和代谢物的信号在统计上是显著不同的。标准曲线的斜率比率最高可变化4倍，但CSI方法的变化略小。

  DOI：

  10.1124/dmd.111.040865

文献信息

• Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives
  作者：P. Raghurama Shetty、G. Shivaraja、G. Krishnaswamy、K. Pruthviraj、Vivek Chandra Mohan、S. Sreenivasa

  DOI：10.14233/ajchem.2020.22583

  日期：——

  In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

  在这项工作中，通过以异喹啉和苯乙酮为原料进行碱催化的菲兹杰反应合成了一些2-苯基喹啉-4-羧酰胺衍生物（5a-j），随后通过POCl3进行C-N偶联反应，并评估它们的体外抗微生物和抗癌活性。新合成化合物的结构通过FT-IR、1H和13C NMR以及质谱分析得以确定。合成的羧酰胺类化合物进行了初步的体外抗菌活性和抗真菌活性测试。抗菌活性的结果与标准抗菌药物（环丙沙星）和抗真菌药物（氟康唑）进行了比较。在测试的化合物中，5d、5f和5h表现出良好的活性，抑制区直径范围为10至25毫米。此外，使用MTT法对两种癌细胞系进行了抗癌活性评定。其中，化合物5b、5d、5f和5h在所有衍生物中显示出良好的抗癌活性。为了将体外结果相关联，对（5a-j）进行了ADME和分子对接研究。ADME性质结果显示，除了5a、5e和5g化合物外，所有化合物都符合五原则。合成化合物的分子对接研究显示出良好的结合亲和力，通过与活性位点上的关键残基以及活性位点内的相邻残基进行氢键相互作用。体外和体内研究结果的比较表明，合成的化合物可能作为潜在的抗微生物和抗癌剂。
• Cinchophen Analogues as Potential CNS Agents
  作者：A. Kar

  DOI：10.1002/jps.2600720931

  日期：1983.9

  Several amides of cinchophen were prepared and evaluated as CNS agents. Compounds III, VII, XII, XIII, and XIV exhibited analgesic activity while I, III, and XIV acted as CNS depressants.

  制备了几种噻吩甲酰胺，并作为中枢神经系统药物进行了评估。化合物III，VII，XII，XIII和XIV表现出止痛活性，而化合物I，III和XIV充当中枢神经系统抑制剂。
• Comparative Study of the Affinity and Metabolism of Type I and Type II Binding Quinoline Carboxamide Analogues by Cytochrome P450 3A4
  作者：Upendra P. Dahal、Carolyn Joswig-Jones、Jeffrey P. Jones

  DOI：10.1021/jm201207h

  日期：2012.1.12

  Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N-dealkylation, O-dealkylation, benzylic hydroxylation, and aromatic hydroxylation. The results demonstrated that type II binding QCA analogues were metabolically less stable (2- to 12-fold) at subsaturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation > benzylic hydroxylation > O-demethylation > aromatic hydroxylation. Finally, for the QCA analogues with aza-heteroaromatic rings, we did not detect metabolism in aza-aromatic rings (pyridine, pyrazine, pyrimidine), indicating that electronegativity of the nitrogen can change regioselectivity in CYP metabolism.