3-(4-chlorophenyl)-2-(((3-(4-methoxyphenyl)isoxazol-5-yl)methyl)thio)quinazolin-4(3H)-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-chlorophenyl)-2-(((3-(4-methoxyphenyl)isoxazol-5-yl)methyl)thio)quinazolin-4(3H)-one
• 英文别名: 3-(4-Chlorophenyl)-2-[[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]methylsulfanyl]quinazolin-4-one；3-(4-chlorophenyl)-2-[[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]methylsulfanyl]quinazolin-4-one
• 化学式: C₂₅H₁₈ClN₃O₃S
• 分子量: 475.955
• InChiKey: UTPMJHPEJCVSJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  93.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氯苯胺 在 potassium carbonate 、 sodium salt of N-methyl toluenesulfonamide 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 3.05h， 生成 3-(4-chlorophenyl)-2-(((3-(4-methoxyphenyl)isoxazol-5-yl)methyl)thio)quinazolin-4(3H)-one
  参考文献：
  名称：

  Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study

  摘要：

  Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC50 (mu M) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC50 0.05 mu M), diclofenac (IC50 0.8 mu M) and indomethacin (IC50 0.49 mu M) reference drugs. They also showed 15-LOX inhibition with IC50 (mu M) 6.21, 433, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC50 2.41 mu M) and Meclofenamate sodium (IC50 5.64 mu) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC50 values of 4.78 mu M and 5.63 mu M, respectively, compared to that of diclofenac sodium (4.86 mu M). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC50 = 0.13 mu M). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.065

文献信息

• Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study
  作者：Ghandoura Moussa、Rana Alaaeddine、Lynn M. Alaeddine、Rasha Nassra、Ahmed S.F. Belal、Azza Ismail、Ahmed F. El-Yazbi、Yasser S. Abdel-Ghany、Aly Hazzaa

  DOI：10.1016/j.ejmech.2017.12.065

  日期：2018.1

  Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC50 (mu M) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC50 0.05 mu M), diclofenac (IC50 0.8 mu M) and indomethacin (IC50 0.49 mu M) reference drugs. They also showed 15-LOX inhibition with IC50 (mu M) 6.21, 433, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC50 2.41 mu M) and Meclofenamate sodium (IC50 5.64 mu) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC50 values of 4.78 mu M and 5.63 mu M, respectively, compared to that of diclofenac sodium (4.86 mu M). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC50 = 0.13 mu M). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products. (C) 2017 Elsevier Masson SAS. All rights reserved.