3-amino-2-pentylquinazolin-4(3H)-one | 120107-47-3

• 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-amino-2-pentylquinazolin-4(3H)-one
• 英文别名: 3-Amino-2-pentyl-3H-quinazolin-4-one；3-amino-2-pentylquinazolin-4-one
• CAS: 120107-47-3
• 化学式: C₁₃H₁₇N₃O
• 分子量: 231.297
• InChiKey: ILADSIHUJQBNCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-amino-2-pentylquinazolin-4(3H)-one 在 tetraphosphorus decasulfide 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以53%的产率得到3-amino-2-pentylquinazoline-4(3H)-thione
  参考文献：
  名称：

  使用 DFT 研究对 2-Pentylquinazolin-4(3H)-one(thione) 衍生物进行合成、抗增殖和抗氧化评估

  摘要：

  目前的研究主要旨在检查一些新型喹唑啉酮（硫酮）衍生物 6-14 的抗增殖和抗氧化活性。目前的工作主要集中在两个方面；首先，比较喹唑啉酮和喹唑啉硫酮衍生物。鉴于所研究化合物的抗增殖（针对两种细胞系，即 HepG2 和 MCF-7）和抗氧化（通过两种方法；ABTS 和 DPPH）活性，最好的喹唑啉硫酮衍生物为 6 和 14，表现出与喹唑啉酮衍生物相当的优异效力分别为 5 和 9。其次，我们比较了包括喹唑啉酮部分（11a-d）在内的四个系列希夫碱的活性。此外，研究了具有各种芳醛腙衍生物（11a-d）类似物的化合物的抗增殖和抗氧化活性。由于扩展的共轭体系，这些化合物表现出的效力随着对位给电子基团的增加（OH > OMe > Cl）而增加。值得注意的是，测试化合物的大部分抗增殖和抗氧化活性结果与 DFT 计算一致。

  DOI：

  10.3390/molecules24203787
• 作为产物：
  描述：

  2-氨基亚苯基肼 在 硫酸 作用下， 反应 6.0h， 生成 3-amino-2-pentylquinazolin-4(3H)-one
  参考文献：
  名称：

  Reddy, P. S. N.; Reddy, P. Pratap, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 763 - 765

  摘要：

  DOI：

文献信息

• Novel quinazoline–chromene hybrids as anticancer agents: Synthesis, biological activity, molecular docking, dynamics and ADME studies
  作者：Feyzi Sinan Tokalı、Halil Şenol、Hande İpek Yetke、Ebru Hacıosmanoğlu‐Aldoğan

  DOI：10.1002/ardp.202300423

  日期：2023.11

  In this study, new quinazoline–chromene hybrid compounds were synthesized. The cytotoxic effects on cell viability of the hybrid compounds were tested against A549 human lung adenocarcinoma and BEAS‐2B healthy bronchial epithelial cell lines in vitro. In addition, the ability of the active compounds to inhibit cell migration was tested. Molecular docking studies were performed to evaluate the ligand–protein interactions, and molecular dynamics simulations were performed to determine the interactions and stability of ligand–protein complexes. In silico absorption, distribution, metabolism, and excretion (ADME) studies were conducted to estimate the drug‐likeness of the compounds. Compounds 4 (IC₅₀ = 51.2 µM) and 5 (IC₅₀ = 44.2 µM) were found to be the most active agents against A549 cells. They are found to be more selective against A549 cells than the reference drug doxorubicin. They also have the ability to significantly inhibit cell migration. They have the best docking scores against epidermal growth factor receptor (EGFR) (−11.300 and −11.226 kcal/mol) and vascular endothelial growth factor receptor 2 (VEGFR2) (−10.987 and −11.247 kcal/mol), respectively. In MD simulations, compounds 4 and 5 have strong hydrogen bond interactions above 80% of simulation times and showed a low ligand root mean square deviation (RMSD) around 2 Å. According to the ADME analysis, compounds 4 and 5 exhibit excellent drug‐likeness and pharmacokinetic characteristics.

  摘要 本研究合成了新的喹唑啉-色烯杂化化合物。在体外测试了混合化合物对 A549 人肺腺癌和 BEAS-2B 健康支气管上皮细胞系细胞活力的细胞毒性作用。此外，还测试了活性化合物抑制细胞迁移的能力。分子对接研究评估了配体与蛋白质之间的相互作用，分子动力学模拟确定了配体与蛋白质复合物的相互作用和稳定性。还进行了吸收、分布、代谢和排泄（ADME）硅学研究，以估计化合物的药物亲和性。研究发现，化合物 4（IC50 = 51.2 µM）和化合物 5（IC50 = 44.2 µM）是对 A549 细胞最有效的药物。与参考药物多柔比星相比，它们对 A549 细胞的选择性更强。它们还能显著抑制细胞迁移。它们与表皮生长因子受体（EGFR）（-11.300 和 -11.226 kcal/mol）和血管内皮生长因子受体 2（VEGFR2）（-10.987 和 -11.247 kcal/mol）的对接得分最高。在 MD 模拟中，化合物 4 和 5 的氢键相互作用强度超过模拟次数的 80%，配体均方根偏差（RMSD）在 2 Å 左右，显示出较低的配体均方根偏差。根据 ADME 分析，化合物 4 和 5 表现出了极佳的药物相似性和药代动力学特征。
• 4-Hydroxy-2-quinolones 126. 1-Hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid hydrazide and its derivatives
  作者：I. V. Ukrainets、A. A. Tkach、E. V. Mospanova、E. N. Svechnikova

  DOI：10.1007/s10593-007-0158-y

  日期：2007.8
• REDDY, P. S. N.;REDDY, P. PRATAP, INDIAN J. CHEM. B, 27,(1988) N, C. 763-765
  作者：REDDY, P. S. N.、REDDY, P. PRATAP

  DOI：——

  日期：——
• Discovery of<i>N</i>-quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents
  作者：Wenjie Xue、Yaling Wang、Xu Lian、Xueyao Li、Jing Pang、Johannes Kirchmair、Kebin Wu、Zunsheng Han、Xuefu You、Hongmin Zhang、Jie Xia、Song Wu

  DOI：10.1080/14756366.2022.2084088

  日期：2022.12.31
• 10.1111/cbdd.14599
  作者：Tokalı, Feyzi Sinan、Şenol, Halil、Ateşoğlu, Şeyma、Akbaş, Fahri

  DOI：10.1111/cbdd.14599

  日期：——

  AbstractIn this study, we synthesized 15 novel quinazoline‐morpholinobenzylideneamino hybrid compounds from methyl anthranilate and we assessed their cytotoxicity via in vitro assays against A549 and BEAS‐2B cell lines. Molecular docking studies were conducted to evaluate the protein‐ligand interactions and inhibition mechanisms on nine different molecular targets, while molecular dynamics (MD) simulations were carried out to assess the stability of the best docked ligand–protein complexes. Additionally, ADME prediction was carried out to determine physicochemical parameters and drug likeness. According to the cytotoxicity assays, compound 1 (IC50 = 2.83 μM) was found to be the most active inhibitor against A549 cells. While the selectivity index (SI) of compound 1 is 29, the SI of the reference drugs paclitaxel and sorafenib, used in this study, are 2.40 and 4.92, respectively. Among the hybrid compounds, 1 has the best docking scores against VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) and EGFR (−10.359 kcal/mol). During MD simulations, compound 1 consistently exhibited strong hydrogen bond interactions with the active sites of VEGFR1 and 2, and these interactions were maintained for more than 90% of the simulation time. Additionally, the RMSD and RMSF values of the ligand–protein complexes exhibited high stability at their minimum levels around 1–2 Å. In conclusion, these findings suggest that compound 1 may be a potent and selective inhibitor candidate for lung cancer treatment and inhibition of VEGFR2, especially.