N-[2-(2,2-Dimethyl-propionylamino)-6-(3,4,5-trimethoxy-phenylethynyl)-quinazolin-4-yl]-2,2-dimethyl-propionamide | 141400-23-9

• 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: N-[2-(2,2-Dimethyl-propionylamino)-6-(3,4,5-trimethoxy-phenylethynyl)-quinazolin-4-yl]-2,2-dimethyl-propionamide
• CAS: 141400-23-9
• 化学式: C₂₉H₃₄N₄O₅
• 分子量: 518.613
• InChiKey: SJAKWPFJQHXOJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.02
• 重原子数：
  38.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111.67
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N-[2-(2,2-Dimethyl-propionylamino)-6-(3,4,5-trimethoxy-phenylethynyl)-quinazolin-4-yl]-2,2-dimethyl-propionamide 在 Pd-BaSO₄ 氢气 作用下， 以 吡啶 为溶剂， 反应 0.33h， 以53%的产率得到N-{2-(2,2-Dimethyl-propionylamino)-6-[(Z)-2-(3,4,5-trimethoxy-phenyl)-vinyl]-quinazolin-4-yl}-2,2-dimethyl-propionamide
  参考文献：
  名称：

  Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines

  摘要：

  6-Substituted 2,4-diaminoquinazolines (1) are good inhibitors of dihydrofolate reductase (DHFR) and effective as growth inhibitors of intact bacterial cells in vitro. The most potent compounds in the in vitro tests were, however, ineffective against a systemic murine infection. Quantitative correlations were obtained between DHFR inhibition and the substituent constant molar refractivity (MR) for 3 of the 4 enzymes studied (Escherichia coli, Streptococcus faecalis, and bovine liver DHFR); for the fourth enzyme (Staphylococcus aureus DHFR) the best correlation was obtained with a combination of MR and the lipophilic parameter pi. The recognition that the conformational properties of the 6-substituent may play a vital role in mediating the binding of 1 to DHFR prompted the synthesis of novel analogues specifically designed to test this hypothesis. From these results it was possible to construct a simple schematic model of the binding site occupied by the 6-substituents; a subsequent molecular modelling study agreed with the features of this model.

  DOI：

  10.1016/0223-5234(92)90054-5
• 作为产物：
  描述：

  3.4.5-三甲氧基苯乙炔 在 copper(l) iodide 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 N-[2-(2,2-Dimethyl-propionylamino)-6-(3,4,5-trimethoxy-phenylethynyl)-quinazolin-4-yl]-2,2-dimethyl-propionamide
  参考文献：
  名称：

  Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines

  摘要：

  6-Substituted 2,4-diaminoquinazolines (1) are good inhibitors of dihydrofolate reductase (DHFR) and effective as growth inhibitors of intact bacterial cells in vitro. The most potent compounds in the in vitro tests were, however, ineffective against a systemic murine infection. Quantitative correlations were obtained between DHFR inhibition and the substituent constant molar refractivity (MR) for 3 of the 4 enzymes studied (Escherichia coli, Streptococcus faecalis, and bovine liver DHFR); for the fourth enzyme (Staphylococcus aureus DHFR) the best correlation was obtained with a combination of MR and the lipophilic parameter pi. The recognition that the conformational properties of the 6-substituent may play a vital role in mediating the binding of 1 to DHFR prompted the synthesis of novel analogues specifically designed to test this hypothesis. From these results it was possible to construct a simple schematic model of the binding site occupied by the 6-substituents; a subsequent molecular modelling study agreed with the features of this model.

  DOI：

  10.1016/0223-5234(92)90054-5