(E)-4-(4-dimethylaminophenyl)-6-(4-dimethylaminostyryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid | 1402085-58-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (E)-4-(4-dimethylaminophenyl)-6-(4-dimethylaminostyryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid
• 英文别名: 4-[4-(dimethylamino)phenyl]-6-[(E)-2-[4-(dimethylamino)phenyl]ethenyl]-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylic acid
• CAS: 1402085-58-8
• 化学式: C₂₃H₂₆N₄O₃
• 分子量: 406.484
• InChiKey: JIEFIMCESQILDI-VGOFMYFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(4-dimethylamino-phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 4.0h， 以67%的产率得到(E)-4-(4-dimethylaminophenyl)-6-(4-dimethylaminostyryl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Computer simulation of the in vitro and in vivo anti-inflammatory activities of dihydropyrimidines acid derivatives through the inhibition of cyclooxygenase-2

  摘要：

  Simulation of virtually designed 20 compounds as COX-2 inhibitors using molecular modelling of protein-ligand interactions to predict drug structure-activity relationship was performed in this study. A synthetic route with a rational chemical approach to (E)-2-oxo-(thio)-4-substituted phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-caboxylic acid was designed and demonstrated. A comparative analysis of antimetabolite drug and corresponding metabolites (virtually designed compounds) provided a better understanding of rational drug design. COX-1(pdb entry: 1eqg) and COX-2(pdb entry: 6cox) enzymes docked with novel ligands were evaluated for binding energies. Lead optimization was performed by computational simulation: methoxy-substituted analogues displayed the highest negative ligand-protein-binding energies. These results prompted us to evaluate in vivo anti-inflammatory activity by carrageenan-induced paw oedema test in rats at a dose of 100 mg/kg. Ibuprofen was administered as standard drug. Lead compounds having significant activity were tested for in vitro cyclooxygenase isoenzyme inhibition assay and found to be more selective towards COX-2 as indicated by COX-2 selective index. The objective of our research is to accept the challenge of discovery of new drug. To ensure the desired target specificity and potency, bioavailability and lack of toxicity, our approach stems out lead generation from virtual screening to their synthesis and ends up with biological assays.

  DOI：

  10.1007/s00044-012-0244-2

文献信息

• Computer simulation of the in vitro and in vivo anti-inflammatory activities of dihydropyrimidines acid derivatives through the inhibition of cyclooxygenase-2
  作者：Raksha Dhankar、Anjali M. Rahatgaonkar、Rakesh Shukla、Mukund Chorghade、Ashutosh Tiwari

  DOI：10.1007/s00044-012-0244-2

  日期：2013.5

  Simulation of virtually designed 20 compounds as COX-2 inhibitors using molecular modelling of protein-ligand interactions to predict drug structure-activity relationship was performed in this study. A synthetic route with a rational chemical approach to (E)-2-oxo-(thio)-4-substituted phenyl-6-styryl-1,2,3,4-tetrahydro-pyrimidine-5-caboxylic acid was designed and demonstrated. A comparative analysis of antimetabolite drug and corresponding metabolites (virtually designed compounds) provided a better understanding of rational drug design. COX-1(pdb entry: 1eqg) and COX-2(pdb entry: 6cox) enzymes docked with novel ligands were evaluated for binding energies. Lead optimization was performed by computational simulation: methoxy-substituted analogues displayed the highest negative ligand-protein-binding energies. These results prompted us to evaluate in vivo anti-inflammatory activity by carrageenan-induced paw oedema test in rats at a dose of 100 mg/kg. Ibuprofen was administered as standard drug. Lead compounds having significant activity were tested for in vitro cyclooxygenase isoenzyme inhibition assay and found to be more selective towards COX-2 as indicated by COX-2 selective index. The objective of our research is to accept the challenge of discovery of new drug. To ensure the desired target specificity and potency, bioavailability and lack of toxicity, our approach stems out lead generation from virtual screening to their synthesis and ends up with biological assays.