| Literature DB >> 17303420 |
Sean T Murphy1, Heather L Case, Edmund Ellsworth, Susan Hagen, Michael Huband, Themis Joannides, Chris Limberakis, Keith R Marotti, Amy M Ottolini, Mark Rauckhorst, Jeremy Starr, Michael Stier, Clarke Taylor, Tong Zhu, Adrian Blaser, William A Denny, Guo-Liang Lu, Jeff B Smaill, Freddy Rivault.
Abstract
Several novel series of nitrile-containing fluoroquinolones with weakly basic amines are reported which have reduced potential for hERG (human ether-a-go-go gene) channel inhibition as measured by the dofetilide assay. The new fluoroquinolones are potent against both Gram-positive and fastidious Gram-negative strains, including Methicillin resistant Staphylococcus aureus and fluoroquinolone-resistant Streptococcus pneumoniae. Several analogs also showed low potential for human genotoxicity as measured by the clonogenicity test. Compounds 22 and 37 (designated PF-00951966 and PF-02298732, respectively), which had good in vitro activity and in vitro safety profiles, also showed good pharmacokinetic properties in rats.Entities:
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Year: 2007 PMID： 17303420 DOI： 10.1016/j.bmcl.2007.01.090
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823