2-[3-(ethyloxy)-4-hydroxyphenyl]quinazolin-4(3H)-one | 1386555-25-4

• 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: 2-[3-(ethyloxy)-4-hydroxyphenyl]quinazolin-4(3H)-one
• 英文别名: 2-(3'-ethoxy-4'-hydroxyphenyl)quinazolin-4(3H)-one；2-(3-ethoxy-4-hydroxyphenyl)-3H-quinazolin-4-one
• CAS: 1386555-25-4
• 化学式: C₁₆H₁₄N₂O₃
• 分子量: 282.299
• InChiKey: ACVBJGJCXIWMBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  乙基香兰素 、 2-氨基苯甲酰胺 在 copper(II) choride dihydrate 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以98%的产率得到2-[3-(ethyloxy)-4-hydroxyphenyl]quinazolin-4(3H)-one
  参考文献：
  名称：

  2-芳基喹唑啉-4（3 H）-ones的合成及β-葡萄糖醛酸苷酶抑制活性

  摘要：

  2- Arylquinazolin-4（3 ħ） -酮1 - 25通过使用的CuCl各种苯甲醛邻氨基苯甲酰胺反应而合成的2 ·2H 2 O作为在回流下在乙醇中的催化剂。评价了合成的2-芳基喹唑啉-4（3 H）-ones 1 – 25的β-葡萄糖醛酸苷酶抑制潜力。观察到IC 50对酶的抑制趋势在0.6–198.2μM的范围内，并与标准d-蔗糖1,4-内酯（IC 50  = 45.75± 2.16μM ）进行了比较。化合物13，19，4，12，14，22，23，25，15，8，17，11，21，1，3，18，9，2，和24与IC 50 0.6-44.0微米的范围内的值，表明该化合物具有具有比标准更高的活性。该化合物对PC-3细胞无细胞毒性作用。建立了结构与活动的关系。

  DOI：

  10.1016/j.bmc.2014.04.039

文献信息

• Antioxidant and ROS Inhibitory Activities of Heterocyclic 2-Aryl-4(3H)-quinazolinone Derivatives
  作者：Shahida Perveen、Syed Muhammad Saad、Khalid Mohammed Khan、Muhammad Iqbal Choudhary

  DOI：10.2174/1570180818666210427092319

  日期：2021.8

  Most of the 2-aryl-4(3H)-quinazolinone derivatives showed potent antioxidant activities in superoxide anion radical scavenging assay with IC50 value ranging between 0.57 μM - 48.93 μM, as compared to positive control quercetin dihydrate (IC50 = 94.1 ± 1.1 μM ). Compounds 5, 6, and 14 showed excellent activity in DPPH assay. Compounds 5-8, 12-15, 17, and 20 showed promising activities in the ROS inhibition

  背景：抗氧化剂是小分子，可防止或延迟由高活性自由基引起的氧化过程。这些分子以其保护各种细胞结构和其他生物分子免受氧化应激和自由基侵害的能力而闻名。因此，抗氧化剂在防止由高活性自由基引起的氧化损伤方面起着关键作用。 方法：在本研究中，通过使用体外 DPPH 和超氧阴离子自由基清除活性筛选了一系列先前合成的杂环 2-芳基-4(3H)-喹唑啉酮衍生物 1-25 的抗氧化活性。还通过血清调理酵母聚糖激活的全血吞噬细胞和分离的中性粒细胞来评估 ROS 抑制活性。通过使用针对 3T3 细胞系的 MTT 测定进行细胞毒性研究。 结果：与阳性对照槲皮素二水合物（IC 50 = 94.1）相比，大多数 2-芳基-4（3H）-喹唑啉酮衍生物在超氧阴离子自由基清除试验中显示出强大的抗氧化活性，IC 50值范围为 0.57 μM - 48.93 μM ± 1.1 微米）。化合物 5、6 和 14 在 DPPH 测定中显示出优异的活性。化合物
• Synthesized 2-Trifluoromethylquinazolines and Quinazolinones Protect BV2 and N2a Cells against LPS- and H2O2-induced Cytotoxicity
  作者：Neeranjini Nallathamby、Chia-Wei Phan、Matej Sova、Luciano Saso、Vikineswary Sabaratnam

  DOI：10.2174/1573406416666191218095635

  日期：2021.7

  Microglia are associated with neuroinflammation, which play a key role in the pathogenesis of neurodegenerative diseases. It has been reported that some quinazolines and quinazolinones possess anti-inflammatory properties. However, the pharmacological properties of certain quinazoline derivatives are still unknown.

  The antioxidant, cytotoxic, and protective effects of a series of synthesized 2- trifluoromethylquinazolines (2, 4, and 5) and quinazolinones (6-8) in lipopolysaccharide (LPS)- murine microglia (BV2) and hydrogen peroxide (H₂O₂)-mouse neuroblastoma-2a (N2a) cells were investigated.

  The antioxidant activity of synthesized compounds was evaluated with ABTS and DPPH assays. The cytotoxic activities were determined by MTS assay in BV2 and N2a cells. The production of nitric oxide (NO) in LPS-induced BV2 microglia cells was quantified.

  The highest ABTS and DPPH scavenging activities were observed for compound 8 with 87.7% of ABTS scavenge percentage and 54.2% DPPH inhibition. All compounds were noncytotoxic in BV2 and N2a cells at 5 and 50 μg/mL. The compounds which showed the highest protective effects in LPS-induced BV2 and H₂O₂-induced N2a cells were 5 and 7. All tested compounds, except 4, also reduced NO production at concentrations of 50 μg/mL. The quinazolinone series 6-8 exhibited the highest percentage of NO reduction, ranging from 38 to 60%. Compounds 5 and 8 possess balanced antioxidant and protective properties against LPS- and H₂O₂-induced cell death, thus showing great potential to be developed into anti-inflammatory and neuroprotective agents.

  Compounds 5 and 7 were able to protect the BV2 and N2a cells against LPS and H₂O₂ toxicity, respectively, at a low concentration (5 μg/mL). Compounds 6-8 showed potent reduction of NO production in BV2 cells.

  背景：微胶质细胞与神经炎症有关，对神经退行性疾病的发病起着关键作用。据报道，一些喹唑啉和喹唑啉酮具有抗炎性能。然而，某些喹唑啉衍生物的药理特性仍未知。 目标：研究一系列合成的2-三氟甲基喹唑啉（2、4和5）和喹唑啉酮（6-8）在脂多糖（LPS）-小鼠微胶质细胞（BV2）和过氧化氢（H₂O₂）-小鼠神经母细胞瘤-2a（N2a）细胞中的抗氧化、细胞毒性和保护作用。 方法：用ABTS和DPPH测定合成化合物的抗氧化活性。通过MTS法测定BV2和N2a细胞的细胞毒性活性。定量测定LPS诱导的BV2微胶质细胞中的一氧化氮（NO）产生量。 结果：化合物8表现出最高的ABTS和DPPH清除活性，ABTS清除率为87.7%，DPPH抑制率为54.2%。所有化合物在5和50 μg/mL浓度下对BV2和N2a细胞均无细胞毒性。在LPS诱导的BV2和H₂O₂诱导的N2a细胞中，表现出最高保护作用的化合物分别为5和7。除4外，所有测试化合物在50 μg/mL浓度下也减少了NO的产生。喹唑啉酮系列6-8表现出最高的NO减少百分比，范围在38%到60%之间。化合物5和8具有平衡的抗氧化和保护性能，对LPS和H₂O₂诱导的细胞死亡具有潜在的抗炎和神经保护作用。 结论：化合物5和7能够以低浓度（5 μg/mL）保护BV2和N2a细胞免受LPS和H₂ O₂的毒性影响。化合物6-8显示出在BV2细胞中强效减少NO产生的作用。
• 2-Arylquinazolin-4(3H)-ones: A novel class of thymidine phosphorylase inhibitors
  作者：Sumaira Javaid、Syed Muhammad Saad、Shahnaz Perveen、Khalid Mohammed Khan、M. Iqbal Choudhary

  DOI：10.1016/j.bioorg.2015.10.006

  日期：2015.12

  Thymidine phosphorylase (TP) over expression plays an important role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. In this regard, a series of twenty-five 2-arylquinazolin-4(3H)-one derivatives 1-25 were evaluated for thymidine phosphorylase inhibitory activity. Six compounds 5, 6, 20, 2, 23, and 3 were found to be active against thymidine phosphorylase enzyme with IC50 values in the range of 42.9-294.6 mu M. 7-Deazaxanthine (IC50 = 41.0 +/- 1.63 mu M) was used as a standard inhibitor. Compound 5 showed a significant activity (IC50 = 42.9 +/- 1.0 mu M), comparable to the standard. The enzyme kinetic studies on the most active compounds 5, 6, and 20 were performed for the determination of their modes of inhibition, and dissociation constants K-i. All active compounds were found to be largely non-cytotoxic against the mouse fibroblast 3T3 cell line. This study identifies a novel class of thymidine phosphorylase inhibitors which may be further investigated as leads to develop therapeutic agents. (C) 2015 Elsevier Inc. All rights reserved.
• Perveen, Shama; Saad, Syed Muhammad; Perveen, Shahnaz, Journal of the Chemical Society of Pakistan, 2016, vol. 38, # 2, p. 352 - 357
  作者：Perveen, Shama、Saad, Syed Muhammad、Perveen, Shahnaz、Hameed, Abdul、Alam, Muhammad Tanveer、Khan, Khalid Mohammed、Choudhary, M. Iqbal

  DOI：——

  日期：——
• US20140256754A1
  申请人：——

  公开号：US20140256754A1

  公开（公告）日：2014-09-11