159018-81-2Relevant academic research and scientific papers
Structure-based design of new DHFR-based antibacterial agents: 7-aryl-2,4-diaminoquinazolines
Li, Xiaoming,Hilgers, Mark,Cunningham, Mark,Chen, Zhiyong,Trzoss, Michael,Zhang, Junhu,Kohnen, Lucy,Lam, Thanh,Creighton, Chris,Gc, Kedar,Nelson, Kirk,Kwan, Bryan,Stidham, Mark,Brown-Driver, Vickie,Shaw, Karen J.,Finn, John
, p. 5171 - 5176 (2011/10/09)
Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4- diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains.
