1335222-93-9Relevant 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.
DIHYDROFOLATE REDUCTASE INHIBITORS
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Page/Page column 21-22, (2011/12/14)
The present disclosure provides compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, wherein R5, R6 and Z are as described herein. The disclosure also provides pharmaceutical compositions thereof; and methods for inhibiting DHFR activity; and methods for treating cell proliferative diseases, autoimmune disease, inflammatory disease or bacterial, fungal or parasitic infection by administering a compound of Formula I.
