methyl 1-(2,4-diaminoquinazolin-7-yl)-2-(thiazol-2-yl)-1H-benzo[d]imidazole-6-carboxylate | 1535186-73-2

• 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: methyl 1-(2,4-diaminoquinazolin-7-yl)-2-(thiazol-2-yl)-1H-benzo[d]imidazole-6-carboxylate
• CAS: 1535186-73-2
• 化学式: C₂₀H₁₅N₇O₂S
• 分子量: 417.451
• InChiKey: HPKVQMVYSGYPGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  30.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  134.83
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  2-醛基噻唑 、 3,4-二氨基苯甲酸甲酯 、 碳酸胍 、 2,4-二氟苯腈 在 氧气 、 溶剂黄146 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 N-甲基吡咯烷酮 为溶剂， 反应 174.33h， 生成 methyl 1-(2,4-diaminoquinazolin-7-yl)-2-(thiazol-2-yl)-1H-benzo[d]imidazole-6-carboxylate 、 methyl 1-(2,4-diaminoquinazolin-7-yl)-2-(thiazol-2-yl)-1H-benzo[d]imidazole-5-carboxylate
  参考文献：
  名称：

  Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines

  摘要：

  A new series of dihydrofolate reductase (DHFR) inhibitors, the 7-(benzimidazol-1-yl)-2,4-diaminoquinazolines, were designed and optimized for antibacterial potency and enzyme selectivity. The most potent inhibitors in this series contained a five-membered heterocycle at the 2-position of, the benzimidazole, leading to highly potent and selective compounds that exploit the differences in the size of a binding pocket adjacent to the NADPH cofactor between the bacterial and human DHFR enzymes. Typical of these compounds is 74(2-thiazol-2-yObenzimidazol-1-yl)-2,4 diaminoquinazoline, which is a potent inhibitor of S. aureus DHFR (K-i = 0.002 nM) with 46700-fold selectivity over human DHFR. This compound also has high antibacterial potency on Gram-positive bacteria with an MIC versus wild type S. aureus of 0.0125 mu g/mL and a MIC versus trimethoprim-resistant S. aureus of 0.25 mu g/mL. In vivo efficacy versus a S. aureus septicemia was demonstrated, highlighting the potential of this new series.

  DOI：

  10.1021/jm401204g