| Literature DB >> 21831637 |
Xiaoming Li1, Mark Hilgers, Mark Cunningham, Zhiyong Chen, Michael Trzoss, Junhu Zhang, Lucy Kohnen, Thanh Lam, Chris Creighton, Kedar G C, Kirk Nelson, Bryan Kwan, Mark Stidham, Vickie Brown-Driver, Karen J Shaw, John Finn.
Abstract
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.Entities:
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Year: 2011 PMID： 21831637 DOI： 10.1016/j.bmcl.2011.07.059
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823