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The synthesis and biological evaluation of novel series of nitrile-containing fluoroquinolones as antibacterial agents.

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Murphy ST,Case HL,Ellsworth E,Hagen S,Huband M,Joannides T,Limberakis C,Marotti KR,Ottolini AM,Rauckhorst M,Starr J,Stier M,Taylor C,Zhu T,Blaser A,Denny WA,Lu GL,Smaill JB,Rivault F

doi

10.1016/j.bmcl.2007.01.090

subject

Has Abstract

pub_date

2007-04-15 00:00:00

pages

2150-5

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)00160-6

journal_volume

17

pub_type

杂志文章

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