N-(4-acetylphenyl)-2-(5-cyano-6-(3-methoxyphenyl)-4-oxo-1,6-dihydropyrimidin-2-ylthio)acetamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)-2-(5-cyano-6-(3-methoxyphenyl)-4-oxo-1,6-dihydropyrimidin-2-ylthio)acetamide
• 英文别名: N-(4-acetylphenyl)-2-[[5-cyano-4-(3-methoxyphenyl)-6-oxo-1H-pyrimidin-2-yl]sulfanyl]acetamide
• 化学式: C₂₂H₁₈N₄O₄S
• 分子量: 434.475
• InChiKey: PWZKDBYJLZTANB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)-2-(5-cyano-6-(3-methoxyphenyl)-4-oxo-1,6-dihydropyrimidin-2-ylthio)acetamide 在 盐酸羟胺 作用下， 以 乙醇 为溶剂， 以60%的产率得到2-(5-cyano-4-(3-methoxyphenyl)-6-oxo-1,6-dihydropyrimidin-2-ylthio)-N-(4-(1-(hydroxyimino)ethyl)phenyl)acetamide
  参考文献：
  名称：

  Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation

  摘要：

  A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI(50) ranging from 19 to 100 mu M and selectivity ratios ranging between 0.75 and 1.71 at the GI(50) level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of -9.80 to -11.25 kcal/mol compared to -12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.

  DOI：

  10.1016/j.bioorg.2020.104090
• 作为产物：
  描述：

  3-甲氧基苯甲醛 在 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 N-(4-acetylphenyl)-2-(5-cyano-6-(3-methoxyphenyl)-4-oxo-1,6-dihydropyrimidin-2-ylthio)acetamide
  参考文献：
  名称：

  Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation

  摘要：

  A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI(50) ranging from 19 to 100 mu M and selectivity ratios ranging between 0.75 and 1.71 at the GI(50) level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of -9.80 to -11.25 kcal/mol compared to -12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.

  DOI：

  10.1016/j.bioorg.2020.104090

文献信息

• Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation
  作者：Adel A. Marzouk、Salah A. Abdel-Aziz、Kamal S. Abdelrahman、Amira S. Wanas、Ahmed M. Gouda、Bahaa G.M. Youssif、Mohamed Abdel-Aziz

  DOI：10.1016/j.bioorg.2020.104090

  日期：2020.9

  A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI(50) ranging from 19 to 100 mu M and selectivity ratios ranging between 0.75 and 1.71 at the GI(50) level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of -9.80 to -11.25 kcal/mol compared to -12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.