5,6-dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazole | 1535186-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5,6-dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazole
• 英文别名: 5,6-Dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazole；5,6-dimethyl-2-(3-methylimidazol-4-yl)-1H-benzimidazole
• CAS: 1535186-74-3
• 化学式: C₁₃H₁₄N₄
• 分子量: 226.281
• InChiKey: BGCKGWYUWDADJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  518.3±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-二氟苯腈 、 5,6-dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazole 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 4-(5,6-dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazol-1-yl)-2-fluorobenzonitrile 、
  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
• 作为产物：
  描述：

  1-甲基-1氢-5-醛基-咪唑 、 4，5-二甲基-1，2-苯二胺 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以53.7%的产率得到5,6-dimethyl-2-(1-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazole
  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

文献信息

• Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines
  作者：Thanh Lam、Mark T. Hilgers、Mark L. Cunningham、Bryan P. Kwan、Kirk J. Nelson、Vickie Brown-Driver、Voon Ong、Michael Trzoss、Grayson Hough、Karen Joy Shaw、John Finn

  DOI：10.1021/jm401204g

  日期：2014.2.13

  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.