3-(4-methoxyphenyl)-1H,3H-quinazolin-2,4-dione | 2400-97-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(4-methoxyphenyl)-1H,3H-quinazolin-2,4-dione
• 英文别名: 3-(4-methoxyphenyl)quinazoline-2,4(1H,3H)-dione；3-(p-Methoxyphenyl)-chinazolin-2,4-dion；3-(4-methoxyphenyl)-1H-quinazoline-2,4-dione
• CAS: 2400-97-7
• 化学式: C₁₅H₁₂N₂O₃
• 分子量: 268.272
• InChiKey: CJAHENZRXKHXSA-UHFFFAOYSA-N

物化性质

• 熔点：
  229 °C(Solv: ethanol, 60% (64-17-5))
• 密度：
  1.311±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-methoxyphenyl)-1H,3H-quinazolin-2,4-dione 在 二硫化碳 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以86%的产率得到2-疏基-3-(4-甲氧基苯基)喹唑啉-4(3h)-酮
  参考文献：
  名称：

  作为酪氨酸酶抑制剂的硫代-2,3-二氢喹唑啉酮衍生物的设计、合成、生物学评价和分子对接研究

  摘要：

  已知酪氨酸酶是黑色素生成和色素沉着过度的关键酶。在这项研究中，设计并合成了一系列硫代二氢喹唑啉酮化合物作为酪氨酸酶抑制剂。在所研究的化合物中，4m表现出最好的抑制活性，IC 50值为 15.48 µM，而曲酸作为阳性对照的 IC 50值为 9.30 µM。在针对酪氨酸酶的动力学评估中，4m描绘了混合抑制模式。此外，抗氧化评估在 2,2-diphenyl-1-picrylhydrazyl (DPPH) 测定中表现出中等至弱的效力。通过分子对接研究解释了最有效衍生物对酪氨酸酶的详细相互作用和结合模式。此外，还进行了计算机辅助药物相似性和药代动力学研究。

  DOI：

  10.1016/j.molstruc.2021.132283
• 作为产物：
  描述：

  2-氨基-N-(4-甲氧基苯基)-苯甲酰胺 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 3-(4-methoxyphenyl)-1H,3H-quinazolin-2,4-dione
  参考文献：
  名称：

  2,4(1H,3H)-喹唑啉二酮和3-取代的2,4(1H,3H)-喹唑啉二酮的合成

  摘要：

  近几十年来，2,4(1H,3H)-喹唑啉二酮因其作为抗惊厥药、精神镇静剂、降血压化合物或嘌呤霉素敏感氨肽酶抑制剂的生物活性而受到关注，显示肿瘤细胞侵袭抑制~nl-~喹唑啉二酮也是有用的合成物杂环化学中的材料。”-5 我们在此报告了一种基于 2-[(三氯乙酰基)氨基]苯甲酰胺环化制备 2,4(1H,3H)-喹唑啉二酮及其 3-取代类似物的新合成方法。该方法包括三个步骤，即 N-取代的 2-氨基苯甲酰胺 1 的合成，后者化合物的三氯乙酰化为 2-[(三氯乙酰基)氨基]苯甲酰胺 2，以及它们的碱基诱导的分子内环化导致 2,4(1H,3H) -喹唑啉二酮 3（方案 1）。

  DOI：

  10.1080/00304940509354986

文献信息

• Green Synthesis of Quinazolinone Derivatives Catalyzed by Iodine in Ionic Liquid
  作者：Shu-Liang Wang、Ke Yang、Chang-Sheng Yao、Xiang-Shan Wang

  DOI：10.1080/00397911.2010.524340

  日期：2012.2.1

  Abstract A series of quinazolinone derivatives were synthesized by the reaction of 2-aminobenzamides and triethyl orthoformate or triphosgene in ionic liquid of [BMIm]BF4 at 80 °C catalyzed by iodine in good yields. Compared to other methods, this new procedure has the advantages of mild reaction conditions, good yields, operational simplicity, and environmentally friendly procedure. GRAPHICAL ABSTRACT

  摘要 在碘催化的[BMIm]BF4离子液体中，2-氨基苯甲酰胺与原甲酸三乙酯或三光气在80℃反应，合成了一系列喹唑啉酮衍生物。与其他方法相比，这种新方法具有反应条件温和、收率好、操作简单、对环境友好等优点。图形概要
• Relationships Between the Chemical Structure of Substances and Their Antimycobacterial Activity Against Atypical Strains. Part 18. 3-Phenyl-2H-1,3-benzoxazine-2,4(3H)-diones and Isosteric 3-Phenylquinazoline-2,4(1H,3H)-diones
  作者：Karel Waisser、Miloš Macháček、Hynek Dostál、Jiří Gregor、Lenka Kubicová、Věra Klimešová、Jiří Kuneš、Karel Palát、Jana Hladůvková、Jarmila Kaustová、Ute Möllmann

  DOI：10.1135/cccc19991902

  日期：——

  A series of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 and 3-phenylquinazoline-2,4(1H,3H)-diones 5 substituted on the phenyl rings were synthesized. The target compounds as well as the intermediates were tested against Mycobacterium tuberculosis, M. kansasii, and M. avium. The replacement of the oxygen atom by nitrogen resulted in a decrease or loss of antimycobacterial activity. 2-[(Ethoxycarbonyl)amino]benzanilides 4 appeared to be inactive. Salicylanilides 1 and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-diones 2 exhibit significant activity against both M. tuberculosis and nontuberculous mycobacteria (the MICs within the range of 4-250 μmol/l for all compounds). The antimycobacterial activity of the compounds increases with increasing both electron-withdrawing properties and hydrophobicity of the substituent(s) on the phenyl moiety. The antimycobacterial profile of the compounds was analyzed according to the criteria based on vector algebra, such as cosine coefficients. Moreover, salicylanilides 1 exhibit activity against other microorganisms tested by the agar diffusion method.

  合成了一系列在苯环上取代的3-苯基-2H-1,3-苯并噁嗪-2,4(3H)-二酮2和3-苯基喹唑啉-2,4(1H,3H)-二酮5。目标化合物以及中间体被测试对抗结核分枝杆菌、肯萨斯分枝杆菌和埃维分枝杆菌。氮原子替代氧原子导致抗结核活性下降或丧失。2-[(乙氧羰基)氨基]苯甲酰胺4似乎无活性。水杨酰苯胺1和3-苯基-2H-1,3-苯并噁嗪-2,4(3H)-二酮2对结核分枝杆菌和非结核分枝杆菌表现出显著活性（所有化合物的最小抑制浓度在4-250 μmol/l范围内）。化合物的抗结核活性随着苯基上取代基的电子吸引性和疏水性增加而增加。根据基于向量代数的标准，如余弦系数，分析了化合物的抗结核特性。此外，水杨酰苯胺1对经琼脂扩散法测试的其他微生物也具有活性。
• Efficient preparation of 3-substituted quinazolinediones directly from anthranilic acids and isocyanates
  作者：Natalie Koay、Louis-Charles Campeau

  DOI：10.1002/jhet.551

  日期：2011.3

  An efficient and practical synthesis of 3‐substituted quinazolinediones is described. The protocol uses readily available isocyanates and anthranilic acids as precursors in a one‐pot operation and has been demonstrated on >50 g scale. Isolation of the products via filtration directly from the reaction media is facile, affording high‐purity material. This procedure was then applied to the synthesis

  描述了一种高效，实用的3-取代喹唑啉二酮的合成方法。该协议在一口操作中使用了现成的异氰酸酯和邻氨基苯甲酸作为前体，并已证明> 50 g规模。通过过滤直接从反应介质中分离产物很容易，从而提供了高纯度的物质。然后将该程序应用于Zenarestat的合成。J.杂环化​​学。（2011）。
• Oxidative Rearrangement of Isatins with Arylamines Using H₂ O₂ as Oxidant: A Facile Synthesis of Quinazoline-2,4-diones and Evaluation of Their Antibacterial Activity
  作者：Guanghao Shi、Xinwei He、Yongjia Shang、Cheng Yang、Liwei Xiang

  DOI：10.1002/cjoc.201700280

  日期：2017.12

  A green and highly efficient synthetic method for the synthesis of quinazoline‐2,4‐diones with hydrogen peroxide as the terminal oxidant has been developed. The reaction features the mild reaction conditions, broad substrate scope, metal‐free catalysts, and sole byproduct water. A plausible mechanism for this process was proposed. Moreover, an antibacterial activity study was performed to evaluate

  开发了一种绿色高效的合成方法，以过氧化氢为末端氧化剂合成喹唑啉-2,4-二酮。该反应具有温和的反应条件，广泛的底物范围，无金属催化剂和唯一的副产物水。为此过程提出了一个合理的机制。此外，还进行了一项抗菌活性研究，以使用肉汤微稀释法评估对两种革兰氏阴性细菌菌株（大肠杆菌和肺炎克雷伯菌）和两种革兰氏阳性细菌菌株（表皮葡萄球菌和金黄色葡萄球菌）的抗菌活性。
• Molecular Modeling Studies and Synthesis of Novel Methyl 2-(2-(4-Oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)alkanoates with Potential Anti-cancer Activity as Inhibitors for Methionine Synthase
  作者：Ismail Mahmoud Elfekki、Walid Fathalla Mohamed Hassan、Hosam Eldin Abd Elhamed Elshihawy、Ibrahim Ahmed Ibrahim Ali、Elsayed Hussein Mostafa Eltamany

  DOI：10.1248/cpb.c14-00158

  日期：——

  Cobalamin-dependant cytosolic enzyme methionine synthase (MetS) catalyses the transfer of a methyl group from the methyltetrahydrofolate (MTHF) to homocysteine (Hcy) to produce methionine and tetrahydrofolate (THF). MetS is over-expressed in the cytosol of certain breast and prostate tumour cells. Methionine used as a source of one carbon atom for the building of the DNA of the tumour cells, structural protein and enzymes. In this study, we designed, synthesized and evaluated the cytotoxic activity of a series of substituted methyl 2-(2-(4-oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)acetate and dipeptide that mimic the substructure of MTHF. These inhibitors were docked in to the MTHF binding domain in such the same way as MTHF in its binding domain. The free energies of the binding were calculated and compared to the IC50 values. This series has been developed by dicyclohexylcarbodiimide (DCC) and azide coupling methods of amino acid esters with carboxylic acid derivatives, respectively. Compound methyl 3-hydroxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)acetamido)propanoate exhibited the highest IC50 value 20 µg/mL against PC-3 cell line and scored the lowest free energy of the binding (−207.19 kJ/mol).

  依赖于钴胺素的细胞膜酶甲硫氨酸合成酶（MetS）催化甲基四氢叶酸（MTHF）的甲基转移到同型半胱氨酸（Hcy）上，生成甲硫氨酸和四氢叶酸（THF）。MetS 在某些乳腺和前列腺肿瘤细胞的细胞质中过度表达。蛋氨酸是构建肿瘤细胞 DNA、结构蛋白和酶的一个碳原子来源。在这项研究中，我们设计、合成并评估了一系列取代 2-(2-(4-氧代-3-芳基-3,4-二氢喹唑啉-2-基硫基)乙酰氨基)乙酸甲酯和二肽的细胞毒性活性，它们模拟了 MTHF 的亚结构。这些抑制剂以与 MTHF 结合域相同的方式与 MTHF 结合域对接。计算出的结合自由能与 IC50 值进行了比较。这一系列化合物分别是通过二环己基碳二亚胺（DCC）和叠氮化物偶联氨基酸酯与羧酸衍生物的方法开发的。化合物 3-羟基-2-(2-(3-(4-甲氧基苯基)-4-氧代-3,4-二氢喹唑啉-2-基硫)乙酰氨基)丙酸甲酯对 PC-3 细胞系的 IC50 值最高，为 20 µg/mL，结合自由能最低（-207.19 kJ/mol）。