(Z)-2,4-diamino-6-(2-phenylethenyl)quinazoline | 141400-20-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (Z)-2,4-diamino-6-(2-phenylethenyl)quinazoline
• 英文别名: 6-[(Z)-2-phenylethenyl]quinazoline-2,4-diamine
• CAS: 141400-20-6
• 化学式: C₁₆H₁₄N₄
• 分子量: 262.314
• InChiKey: QJACNYODQYNYRG-SREVYHEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-[2-(2,2-Dimethyl-propionylamino)-6-phenylethynyl-quinazolin-4-yl]-2,2-dimethyl-propionamide 在 Pd-BaSO₄ 盐酸 、 氢气 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 3.33h， 生成 (Z)-2,4-diamino-6-(2-phenylethenyl)quinazoline
  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

文献信息

• Antifolate and antibacterial activities of 6-substituted 2,4-diaminoquinazolines
  作者：NV Harris、C Smith、K Bowden

  DOI：10.1016/0223-5234(92)90054-5

  日期：1992.1

  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.