2-(2-甲基-4-氧代-3(4H)-喹唑啉基)苯甲酸 | 4005-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 2-(2-甲基-4-氧代-3(4H)-喹唑啉基)苯甲酸
• 英文名称: 2-(2-methyl-4-oxo-4H-quinazolin-3-yl)-benzoic acid
• 英文别名: 2-<2-methyl-4(3H)-oxo-3-quinazolinyl> benzoic acid；2-(2-methyl-4-oxoquinazolin-3(4H)-yl)benzoic acid；3-(2-carboxyphenyl)-2-methylquinazolin-4(3H)-one；2-(2-methyl-4-oxoquinazolin-3-yl)benzoic acid；2-(2-methyl-4-oxo-4H-quinazolin-3-yl)-benzoic acid；2-(2-Methyl-4-oxo-4H-chinazolin-3-yl)-benzoesaeure
• CAS: 4005-06-5
• 化学式: C₁₆H₁₂N₂O₃
• 分子量: 280.283
• InChiKey: NVCRIJIVAAYRER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(2-甲基-4-氧代-3(4H)-喹唑啉基)苯甲酸 在 zinc(II) chloride 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 6-(anilinomethyl)-6H-quinolino[2,1-b]quinazoline-5,12-dione
  参考文献：
  名称：

  Saxena, Sushma; Verma, M; Saxena, A K, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1991, vol. 30, # 4, p. 453 - 456

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基吲哚-3-甲醛 在 Oxone 作用下， 以 水 、 乙腈 为溶剂， 反应 16.0h， 以84%的产率得到2-(2-甲基-4-氧代-3(4H)-喹唑啉基)苯甲酸
  参考文献：
  名称：

  Formation of tryptanthrin compounds upon Oxone-induced dimerization of indole-3-carbaldehydes

  摘要：

  Tryptanthrin is a natural product with numerous important pharmacological properties. Tryptanthrin and its analogs are commonly prepared by condensation of isatoic anhydride and isatin. In this Letter we investigate the formation of tryptanthrin derivatives upon Oxone-induced oxidative dimerization of indole-3-carbaldehydes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.09.124

文献信息

• Screening of Natural Deep Eutectic Solvents for Green Synthesis of 2-methyl-3-substituted Quinazolinones and Microwave-Assisted Synthesis of 3-aryl Quinazolinones in Ethanol
  作者：Mario Komar、Maja Molnar、Anastazija Konjarević

  DOI：10.5562/cca3597

  日期：——

  In this study, two fast and efficient protocols for green synthesis of 3-substituted quinazolinones were perfomed. A synthesis of 2-methyl-3-substituted quinazolinones was performed in natural deep eutectic solvents, while 3-aryl quinazolinones were obtained by using microwave assisted synthesis. Benzoxazinone, which was used as an intermediate in the synthesis of 2-methyl-3-substituted quinazolinones, was prepared conventionally from anthranilic acid and acetic anhydride. In order to find the most appropriate synthetic path, twenty natural deep eutectic solvents were applied as a solvent in these syntheses. Choline chloride:urea (1 : 2) was found to be the most efficient solvent and was further used in the synthesis of 2-methyl quinazolinone derivatives (2–12). 3-Aryl quinazolinones (13–17), on the other hand, were synthesized in one-pot microwave-assisted reaction of anthranilic acid, different amines and trimethyl orthoformate. All compounds were synthesized in good to excellent yields, characterized by LC-MS/MS spectrometry and 1H- and 13C-NMR spectroscopy.

  本研究采用两种快速高效的方法绿色合成 3-取代喹唑啉酮。在天然深共晶溶剂中合成了 2-甲基-3-取代喹唑啉酮，而通过微波辅助合成获得了 3-芳基喹唑啉酮。合成 2-甲基-3-取代喹唑啉酮的中间体苯并噁嗪酮是用蚁酸和乙酸酐通过传统方法制备的。为了找到最合适的合成途径，在这些合成中使用了 20 种天然深共晶溶剂作为溶剂。结果发现氯化胆碱：脲（1:2）是最有效的溶剂，并被进一步用于合成 2-甲基喹唑啉酮衍生物 (2-12)。另一方面，3-芳基喹唑啉酮（13-17）是在蚁酸、不同的胺和原甲酸三甲酯的微波辅助反应中一锅合成的。所有化合物均以良好至极佳的收率合成，并通过 LC-MS/MS 光谱法以及 1H 和 13C-NMR 光谱法进行了表征。
• Exploration of the Structural Space in 4(3<i>H</i>)-Quinazolinone Antibacterials
  作者：Yuanyuan Qian、Giuseppe Allegretta、Jeshina Janardhanan、Zhihong Peng、Kiran V. Mahasenan、Elena Lastochkin、Melissa Malia N. Gozun、Sara Tejera、Valerie A. Schroeder、William R. Wolter、Rhona Feltzer、Shahriar Mobashery、Mayland Chang

  DOI：10.1021/acs.jmedchem.0c00153

  日期：2020.5.28

  the syntheses of 79 derivatives of the 4(3H)-quinazolinones and their structure-activity relationship (SAR) against methicillin-resistant Staphylococcus aureus (MRSA). Twenty one analogs were further evaluated in in vitro assays. Subsequent investigation of the pharmacokinetic properties singled out compound 73 ((E)-3-(5-carboxy-2-fluorophenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one) for further study

  我们在此报告了4（3H）-喹唑啉酮的79种衍生物的合成及其对耐甲氧西林的金黄色葡萄球菌（MRSA）的结构活性关系（SAR）。在体外测定中进一步评估了二十一种类似物。随后的药代动力学研究表明，化合物73（（E）-3-（5-羧基-2-氟苯基）-2-（4-氰基苯乙烯基）喹唑啉-4（3H）-一）进一步研究。在临床相关的MRSA感染小鼠模型中，该化合物在体外和体内均与哌拉西林-他唑巴坦（TZP）协同作用。TZP组合缺乏抗MRSA的活性，但与化合物73协同作用以杀菌方式杀死MRSA。喹唑啉酮类药物与青霉素结合蛋白（PBP）2a的变构位点结合的能力使协同作用合理化，导致活性位点的开放，从而使β-内酰胺抗生素现在能够以其作用机理与活性位点结合。该组合可有效治疗MRSA感染，为此许多抗生素（包括TZP）已面临临床淘汰。
• Synthesis and evaluation of new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives as potent antibacterial agents effective against multidrug resistant Staphylococcus aureus
  作者：Srikanth Gatadi、Jitendra Gour、Manjulika Shukla、Grace Kaul、Swetarka das、Arunava Dasgupta、Y.V. Madhavi、Sidharth Chopra、Srinivas Nanduri

  DOI：10.1016/j.bioorg.2018.11.007

  日期：2019.3

  demonstrate selective and potent inhibitory activity against Staphylococcus aureus (MICs = 0.25–0.5 µg/mL). When tested against Vero cells, all the compounds were found to be non toxic possessing favourable selectivity index (SI > 10), which encouraged us for carrying out further studies. Compound 6′a (SI > 40) was tested against a number of multiple clinical strains of multi-drug resistant S. aureus and was

  由于多种药物耐药性的出现，医院和社区获得性金黄色葡萄球菌感染的治疗变得更具挑战性。这刺激了对快速开发可有效消除耐药机制的新治疗剂的需求。在我们目前的工作中，合成了几种新的4-氧代喹唑啉-3（4 H）-基）苯甲酸和苯甲酰胺衍生物，并检查了它们对ESKAP病原体组和病原性分枝杆菌的抗菌活性。在初步筛选中，化合物4a，4b，6'a，6'b，6'h，6'i和6'j被发现对金黄色葡萄球菌具有选择性和有效的抑制活性（MIC = 0.25–0.5  µg / mL）。当针对Vero细胞进行测试时，发现所有化合物都是无毒的，具有良好的选择性指数（SI> 10），这鼓励我们开展进一步的研究。针对多种具有多重耐药性的金黄色葡萄球菌的多种临床菌株测试了化合物6'a（SI> 40），发现该化合物表现出有效的活性，而与菌株的耐药状态无关。此外，化合物6'a还表现出浓度依赖性的杀菌活性，并与FDA批准的测试药物协同作
• Semi-synthesis and structural elucidation of brevicanines A–D, four new C19-diterpenoid alkaloids with rotameric phenomenon from Aconitum brevicalcaratum
  作者：Zhong-Sheng Wang、Wei Chen、Hai-Yue Jiang、Feng Gao、Xian-Li Zhou

  DOI：10.1016/j.fitote.2019.03.012

  日期：2019.4

  Four new C19-diterpenoid alkaloids brevicanines A-D (1-4) with rotameric phenomenon were isolated from Aconitum brevicalcaratum. They all possessed an unusual axial chiral phenyl-quinazoline side chain and their structures were elucidated by extensive spectroscopic analysis and chemical methods. Meanwhile, brevicanines A and B were semi-synthesized from their parent compound scaconine to further confirm

  从乌头乌头中分离出四个具有旋转现象的新的C19-二萜生物碱brevicanines AD（1-4）。它们都具有不寻常的轴向手性苯基-喹唑啉侧链，并且通过广泛的光谱分析和化学方法阐明了它们的结构。同时，从其母体化合物斯卡可宁中半合成了brevicanines A和B，以进一步确认其结构。还使用可变温度NMR光谱研究了短素卡因A的阻转异构体，其中在室温下在1H NMR光谱中观察到两组信号，并在140°C上合并。这是第一次确定二萜类生物碱的阻转异构性。
• Serventi; Marchesi, Bollettino Scientifico della Facolta di Chimica Industriale di Bologna, 1957, vol. 15, p. 114
  作者：Serventi、Marchesi

  DOI：——

  日期：——