2-chloro-N-(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-yl)acetamide | 1150095-01-4

• 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-chloro-N-(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-yl)acetamide
• CAS: 1150095-01-4
• 化学式: C₁₇H₁₄ClN₃O₃
• 分子量: 343.769
• InChiKey: CLRBMBRZHVVPPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73.22
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  苯胺 、 2-chloro-N-(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-yl)acetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66 %的产率得到N‐(4‐oxo‐2‐(phenoxymethyl)quinazolin‐3(4H)‐yl)‐2‐(phenylamino)acetamide
  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
• 作为产物：
  描述：

  2-(2-苯氧基乙酰氨基)苯甲酸甲酯 在 一水合肼 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 生成 2-chloro-N-(4-oxo-2-(phenoxymethyl)quinazolin-3(4H)-yl)acetamide
  参考文献：
  名称：

  Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma

  摘要：

  DOI：

  10.1080/14756366.2022.2036985

文献信息

• Synthesis and Anticonvulsant Activity of Some Quinazolin-4-(3H)-one Derivatives
  作者：Hanan Georgey、Nagwa Abdel-Gawad、Safinaz Abbas

  DOI：10.3390/molecules13102557

  日期：——

  ) quinazolin-4(3H)-one derivatives 4a,b, 5a-c, 6, 7a-f, 8a-e and 9a,b have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR, MS). A preliminary evaluation of the anticonvulsant activity of the prepared compounds has indicated that compounds 4b, 7b-f, 8a and 9b exhibit significant anticonvulsant activity, while compounds

  已经合成了许多3-取代的-2-（取代的苯氧基甲基）喹唑啉-4（3H）-一衍生物4a，b，5a-c，6，7a-f，8a-e和9a，b。在元素分析和光谱研究（IR，1H-NMR，MS）的基础上阐明了它们的结构。对制备的化合物的抗惊厥活性的初步评估表明，化合物4b，7b-f，8a和9b表现出显着的抗惊厥活性，而化合物6、8b和8d表现出轻度至中度活性。