6,7-dimethoxy-2-(N-phenylamino)quinazolin-4-one | 20198-40-7

• 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: 6,7-dimethoxy-2-(N-phenylamino)quinazolin-4-one
• 英文别名: 2-anilino-6,7-dimethoxy-3H-quinazolin-4-one；2-anilino-6,7-dimethoxy-3H-quinazolin-4-one
• CAS: 20198-40-7
• 化学式: C₁₆H₁₅N₃O₃
• 分子量: 297.313
• InChiKey: SJCPXAHOTBLVFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 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：
  72
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-2-(N-phenylamino)quinazolin-4-one 、 4-溴丁酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 以77%的产率得到4-(6,7-Dimethoxy-2-phenylamino-quinazolin-4-yloxy)-butyric acid ethyl ester
  参考文献：
  名称：

  替代异喹啉和喹唑啉作为潜在的抗炎药。肿瘤坏死因子α抑制剂的合成及生物学评价。

  摘要：

  制备了一系列异喹啉-1-酮和喹唑啉-4-酮及其相关衍生物，并评估了它们抑制细菌脂多糖（LPS）刺激的人外周血单核细胞中肿瘤坏死因子α（TNFα）产生的能力。为了优化TNFα抑制活性，制备了一系列同源的N-链烷酸酯。还进行了几次亲电和亲核取代。发现在异喹啉和喹唑啉系列中，四个碳的链烷酸酯对于活性是最佳的。异喹啉环上的环取代基（如氟，溴，硝基，乙酰基和氨基甲基）导致活性显着下降。同样，喹唑啉环上的相似基团也降低了抑制活性。然而，6和7-氨基喹唑啉衍生物75和76是有效的抑制剂，在TNFalpha体外测定中，每种IC的IC（50）值约为5 microM。然后将小鼠体内肺炎症模型用于评估在初步体外试验中鉴定出的有希望的候选化合物。在该吸入模型中选择了化合物75进行进一步研究，发现化合物75可将LPS处理小鼠的支气管肺泡灌洗液中的TNFα水平降低至对照小鼠的TNFα水平的约50％。因此，在临床相关的

  DOI：

  10.1021/jm9805900
• 作为产物：
  描述：

  2,4-二氯-6,7-二甲氧基喹唑啉 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 6,7-dimethoxy-2-(N-phenylamino)quinazolin-4-one
  参考文献：
  名称：

  Design and synthesis of 2-(arylamino)-4(3H)-quinazolinones as novel inhibitors of rat lens aldose reductase

  摘要：

  A number of 2-(arylamino)-4(3H)-quinazolinones (2a-i) that possess several of the pharmacophore moieties necessary for binding to the inhibitor site of the enzyme aldose reductase were synthesized and tested for their ability to inhibit crude aldose reductase obtained from rat lens. Only those quinazolinones that possess an acidic moiety on the 2-(arylamino) substituent were found to display significant inhibitory activity. Of these, the most potent compound is the 4'-CO2H derivative (2i) with an IC50 of 34 microM, while the least potent is the 4'-OH derivative (2c) with an IC50 of 75 microM. All of the 2-(arylamino)-4(3H)-quinazolinones tested are less potent than other known inhibitors of aldose reductase, such as alrestatin and sorbinil, indicating that the pharmacophore moieties present in these compounds may not be positioned optimally relative to one another for maximal interaction with the enzyme.

  DOI：

  10.1021/jm00155a007

文献信息

• Regioselective synthesis and biological evaluation of<i>N</i>-substituted 2-aminoquinazolin-4-ones
  作者：Zhen-Yuan Liao、Wen-Hsiung Yeh、Pen-Yuan Liao、Yu-Ting Liu、Ying-Cheng Chen、Yi-Hung Chen、Tsung-Han Hsieh、Chia-Chi Lin、Ming-Hsuan Lu、Yi-Song Chen、Ming-Chih Hsu、Tsai-Kun Li、Tun-Cheng Chien

  DOI：10.1039/c8ob00624e

  日期：——

  the Dimroth rearrangement in aqueous ethanolic sodium hydroxide gave exclusively the regioisomers, 2-(N-arylamino)quinazolin-4-ones. The regioselective synthesis of N-aryl-substituted 2-aminoquinazolin-4-ones can be further applied to the synthesis of benzimidazo[2,1-b]quinazolin-12-ones.

  在对-TsOH存在下，在t- BuOH中，在回流下，邻氨基苯甲酸甲酯与N-芳基氰酰胺的反应主要得到3-芳基喹唑啉-4-酮。相比之下，相同的反应物与TMSCl在60°C的t- BuOH中反应，然后在乙醇氢氧化钠水溶液中进行Dimroth重排，仅得到区域异构体2-（N-芳基氨基）喹唑啉-4-酮。N-芳基取代的2-氨基喹唑啉-4-酮的区域选择性合成可以进一步应用于苯并咪唑并[2，1- b ]喹唑啉-12-酮的合成。
• DERUITER, J.;BRUBAKER, A. N.;MILLEN, J.;RILEY, T. N., J. MED. CHEM., 1986, 29, N 5, 627-629
  作者：DERUITER, J.、BRUBAKER, A. N.、MILLEN, J.、RILEY, T. N.

  DOI：——

  日期：——
• Substituted Isoquinolines and Quinazolines as Potential Antiinflammatory Agents. Synthesis and Biological Evaluation of Inhibitors of Tumor Necrosis Factor α
  作者：Qi Chao、Lynn Deng、Hsiencheng Shih、Lorenzo M. Leoni、Davide Genini、Dennis A. Carson、Howard B. Cottam

  DOI：10.1021/jm9805900

  日期：1999.9.1

  mice. Thus, compounds such as 75, which can effectively inhibit proinflammatory cytokines such as TNFalpha in clinically relevant animal models of inflammation and fibrosis, may have potential as new antiinflammatory agents. Finally, a quinazoline derivative suitable to serve as a photoaffinity radiolabeled compound was prepared to help identify the putative cellular target(s) for these TNFalpha inhibitors

  制备了一系列异喹啉-1-酮和喹唑啉-4-酮及其相关衍生物，并评估了它们抑制细菌脂多糖（LPS）刺激的人外周血单核细胞中肿瘤坏死因子α（TNFα）产生的能力。为了优化TNFα抑制活性，制备了一系列同源的N-链烷酸酯。还进行了几次亲电和亲核取代。发现在异喹啉和喹唑啉系列中，四个碳的链烷酸酯对于活性是最佳的。异喹啉环上的环取代基（如氟，溴，硝基，乙酰基和氨基甲基）导致活性显着下降。同样，喹唑啉环上的相似基团也降低了抑制活性。然而，6和7-氨基喹唑啉衍生物75和76是有效的抑制剂，在TNFalpha体外测定中，每种IC的IC（50）值约为5 microM。然后将小鼠体内肺炎症模型用于评估在初步体外试验中鉴定出的有希望的候选化合物。在该吸入模型中选择了化合物75进行进一步研究，发现化合物75可将LPS处理小鼠的支气管肺泡灌洗液中的TNFα水平降低至对照小鼠的TNFα水平的约50％。因此，在临床相关的
• Design and synthesis of 2-(arylamino)-4(3H)-quinazolinones as novel inhibitors of rat lens aldose reductase
  作者：Jack DeRuiter、Abram N. Brubaker、Jane Millen、Thomas N. Riley

  DOI：10.1021/jm00155a007

  日期：1986.5

  A number of 2-(arylamino)-4(3H)-quinazolinones (2a-i) that possess several of the pharmacophore moieties necessary for binding to the inhibitor site of the enzyme aldose reductase were synthesized and tested for their ability to inhibit crude aldose reductase obtained from rat lens. Only those quinazolinones that possess an acidic moiety on the 2-(arylamino) substituent were found to display significant inhibitory activity. Of these, the most potent compound is the 4'-CO2H derivative (2i) with an IC50 of 34 microM, while the least potent is the 4'-OH derivative (2c) with an IC50 of 75 microM. All of the 2-(arylamino)-4(3H)-quinazolinones tested are less potent than other known inhibitors of aldose reductase, such as alrestatin and sorbinil, indicating that the pharmacophore moieties present in these compounds may not be positioned optimally relative to one another for maximal interaction with the enzyme.