3-[(4-Bromophenyl)methylideneamino]-2-(phenoxymethyl)quinazolin-4-one

• 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-Bromophenyl)methylideneamino]-2-(phenoxymethyl)quinazolin-4-one
• 化学式: C₂₂H₁₆BrN₃O₂
• 分子量: 434.3
• InChiKey: QBEJLGLDYKAEEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  54.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对溴苯甲醛 、 3-amino-2-(phenoxymethyl)quinazolin-4(3H)-one 在 哌啶 作用下， 以 乙醇 为溶剂， 以65 %的产率得到3-[(4-Bromophenyl)methylideneamino]-2-(phenoxymethyl)quinazolin-4-one
  参考文献：
  名称：

  Exploring new quinazolin‐4(3H)‐one derivatives as CDK2 inhibitors: Design, synthesis, and anticancer evaluation

  摘要：

  In the present work, five series of new 2,3‐disubstituted quinazolin‐4(3H)‐ones 4a–c, 5a–d, 6a–g, 7a,b, and 9a–c were designed, synthesized, and screened in vitro for their cytotoxic activity against 60 cancer cell lines by the National Cancer Institute, USA. Five candidates 4c, 6a, 6b, 6d, and 6g revealed promising cytotoxicity with significant percentage growth inhibition in the range of 81.98%–96.45% against the central nervous system (CNS) (SNB‐19), melanoma (MDA‐MB‐435), and non‐small cell lung cancer (HOP‐62) cell lines. The in vitro cytotoxic half maximal inhibitory concentration (IC₅₀) values for the most active compounds 4c, 6a, 6b, 6d, and 6g against the most sensitive cell lines were evaluated. Additionally, screening their cyclin‐dependent kinase 2 (CDK2) inhibitory activity was performed. Ortho‐chloro‐benzylideneamino derivative 6b emerged as the most potent compound with IC₅₀ = 0.67 µM compared to Roscovitine (IC₅₀ = 0.64 µM). The most active candidates arrested the cell cycle at G1, S phases, or both, leading to cell death and inducing apoptosis against CNS (SNB‐19), melanoma (MDA‐MB‐435), and non‐small cell lung cancer (HOP‐62) cell lines. The molecular docking study verified the resulting outcomes for the most active candidates in the CDK2‐binding pocket. Finally, physicochemical, and pharmacokinetic properties deduced that compounds 4c, 6a, 6b, 6d, and 6g displayed significant drug‐likeness properties. According to the obtained results, the newly targeted compounds are regarded as promising scaffolds for the continued development of novel CDK2 inhibitors.

  DOI：

  10.1002/ddr.22163