3-(4-methoxyphenyl)-2-(prop-2-yn-1-ylthio)quinazolin-4(3H)-one | 330179-93-6

• 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-methoxyphenyl)-2-(prop-2-yn-1-ylthio)quinazolin-4(3H)-one
• 英文别名: 3-(4-methoxyphenyl)-2-(prop-2-yn-1-ylsulfanyl)quinazolin-4(3H)-one；3-(4-methoxyphenyl)-2-prop-2-ynylsulfanylquinazolin-4-one
• CAS: 330179-93-6
• 化学式: C₁₈H₁₄N₂O₂S
• 分子量: 322.387
• InChiKey: SJRPUWRGVOMVIY-UHFFFAOYSA-N

物化性质

• 熔点：
  193-194 °C(Solv: ethanol (64-17-5))
• 沸点：
  502.6±60.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-methoxyphenyl)-2-(prop-2-yn-1-ylthio)quinazolin-4(3H)-one 、 叠氮苯 在 copper(ll) sulfate pentahydrate 、 维生素 C 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以79%的产率得到3-(4-methoxyphenyl)-2-(((1-phenyl-1H-1,2,3-triazol-4-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
• 作为产物：
  描述：

  甲氧苯胺 在 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-(4-methoxyphenyl)-2-(prop-2-yn-1-ylthio)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 quinazolin-2-yl 1,2,3-triazole hybrids as promising multi-target anticancer agents: Design, synthesis, and molecular docking study
  作者：Noura F.M. El Hamaky、Abdelrahman Hamdi、Waleed A. Bayoumi、Abdullah A. Elgazar、Magda N.A. Nasr

  DOI：10.1016/j.bioorg.2024.107437

  日期：2024.7

  In our study, a series of quinazoline-1,2,3-triazole hybrids () have been designed and synthesized as multi-target EGFR, VEGFR-2, and Topo II inhibitors. All synthesized hybrids were assessed for their anticancer capacity. MTT assay revealed that compounds , , and were the most potent hybrids against four cancer cell lines, HeLa, HePG-2, MCF-7, and HCT-116 at low micromolar range while exhibiting good

  在我们的研究中，一系列喹唑啉-1,2,3-三唑杂化物()被设计和合成为多靶点EGFR、VEGFR-2和Topo II抑制剂。所有合成的杂交体都被评估其抗癌能力。 MTT 测定表明，化合物 、 、 和 是在低微摩尔范围内针对四种癌细胞系 HeLa、HePG-2、MCF-7 和 HCT-116 最有效的杂合体，同时对正常细胞系 WI-38 表现出良好的选择性。随后，评估了这三种化合物的 EGFR、VEGFR-2 和 Topo II 抑制作用。与厄洛替尼 (IC 0.049 µM) 相比，该化合物是中度 EGFR 抑制剂 (IC 0.103 µM)，与索拉非尼 (IC 0.031 µM) 相比，该化合物是良好的 VEGFR-2 抑制剂 (IC 0.069 µM)，与索拉非尼 (IC 0.031 µM) 相比，该化合物是更强的 Topo II 抑制剂 (IC 19.74 µM)。依托泊苷 (IC 34
• Synthesis, properties, and mass-spectrometric fragmentation of 2-thio derivatives of 3-arylquinazolin-4-ones
  作者：Yu. A. Azev、B. V. Golomolzin、T. Dyulcks、N. A. Klyuev、Yu. G. Yatluk

  DOI：10.1007/s10593-007-0052-7

  日期：2007.3