3-(4-methylphenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinan-4-one | 1376299-01-2

• 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-methylphenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinan-4-one
• 英文别名: 3-(4-Methylphenyl)-2-(4-methylsulfonylphenyl)-1,2-dihydroquinazolin-4-one；3-(4-methylphenyl)-2-(4-methylsulfonylphenyl)-1,2-dihydroquinazolin-4-one
• CAS: 1376299-01-2
• 化学式: C₂₂H₂₀N₂O₃S
• 分子量: 392.478
• InChiKey: QBZVBEGQOWKIBV-UHFFFAOYSA-N

物化性质

• 沸点：
  657.4±55.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  乙烷,三氯氟- 在 potassium peroxymonosulfate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 10.0h， 生成 3-(4-methylphenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinan-4-one
  参考文献：
  名称：

  Analogue-based design, synthesis and docking of non-steroidal anti-inflammatory agents. Part 2: Methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-ones

  摘要：

  A series of methyl sulfanyl/methyl sufonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one were designed using analogue-based design, scaffold hopping and shape similarity matching. The designed compounds were synthesized in 2-3 steps with simple chemistry and screened by ovine cyclooxygenases (COXs) inhibitory assay and carrageenan-induced rat paw edema assay. Among the screened compounds, two compounds exhibited 100% cyclooxygenase-2 (COX-2) inhibitory potency without showing cycloxygenase-1 (COX-1) inhibition at 20 mu M. The compounds also showed promising in vivo anti-inflammatory potential. A structure-activity relationship within the dataset was established by correlating the effect of aromatic ring substituent constants, structural variables and physico-chemical descriptors with in vivo anti-inflammatory activity. Molecular docking studies were also performed on the title compounds to study the binding interactions to COX-2 active site residues. The experimentally determined COX-2 inhibitory activity was found moderately correlating with binding modes predicted for compounds by Glide XP dock scoring function. The 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one pharmacophore reported herein should be a new lead for further development of novel non-steroidal anti-inflammatory agents. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.069

文献信息

• Design and Synthesis of New 1,3-Benzdiazinan-4-one Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors
  作者：Afshin Zarghi、Tannaz Zebardast、Fatemeh Hajighasemali、Eskandar Alipoor、Bahram Daraie、Mehdi Hedayati

  DOI：10.1002/ardp.201100138

  日期：2012.4

  A new group of regioisomeric 2,3‐diaryl‐1,3‐benzdiazinan‐4‐ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase‐2 (COX‐2) inhibitory activity. In vitro COX‐1/COX‐2 inhibition studies identified 3‐(p‐fluorophenyl)‐2‐(4‐methylsulfonylphenyl)‐1,3‐benzdiazinane‐4‐one (2b) as a potent and highly selective (IC50 = 0.07 µM; selectivity

  合成了一组具有甲基磺酰基药效团的新区域异构体 2,3-二芳基-1,3-苯并二嗪喃-4-酮，并测试了它们的生物活性的环氧合酶-2 (COX-2) 抑制活性。体外 COX-1/COX-2 抑制研究发现 3-(p-fluorophenyl)-2-(4-methylsulfonylphenyl)-1,3-benzdiazinane-4-one (2b) 是一种有效且高度选择性的药物（IC50 = 0.07 µM；选择性指数 = 572.8) COX-2 抑制剂。
• Analogue-based design, synthesis and docking of non-steroidal anti-inflammatory agents. Part 2: Methyl sulfanyl/methyl sulfonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-ones
  作者：E. Manivannan、S.C. Chaturvedi

  DOI：10.1016/j.bmc.2012.09.069

  日期：2012.12

  A series of methyl sulfanyl/methyl sufonyl substituted 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one were designed using analogue-based design, scaffold hopping and shape similarity matching. The designed compounds were synthesized in 2-3 steps with simple chemistry and screened by ovine cyclooxygenases (COXs) inhibitory assay and carrageenan-induced rat paw edema assay. Among the screened compounds, two compounds exhibited 100% cyclooxygenase-2 (COX-2) inhibitory potency without showing cycloxygenase-1 (COX-1) inhibition at 20 mu M. The compounds also showed promising in vivo anti-inflammatory potential. A structure-activity relationship within the dataset was established by correlating the effect of aromatic ring substituent constants, structural variables and physico-chemical descriptors with in vivo anti-inflammatory activity. Molecular docking studies were also performed on the title compounds to study the binding interactions to COX-2 active site residues. The experimentally determined COX-2 inhibitory activity was found moderately correlating with binding modes predicted for compounds by Glide XP dock scoring function. The 2,3-diaryl-2,3-dihydro-1H-quinazolin-4-one pharmacophore reported herein should be a new lead for further development of novel non-steroidal anti-inflammatory agents. (C) 2012 Elsevier Ltd. All rights reserved.