title: Novel oxazolidinone-quinolone hybrid antimicrobials.
abstract: Antimicrobial compounds incorporating oxazolidinone and quinolone pharmacophore substructures have been synthesized and evaluated. Representative analogues 2, 5, and 6 display an improved potency versus linezolid against gram-positive and fastidious gram-negative pathogens. The compounds are also active against linezolid- and ciprofloxacin-resistant Staphylococcus aureus and Enterococcus faecium strains. The MOA for these new antimicrobials is consistent with a combination of protein synthesis and gyrase A/topoisomerase IV inhibition, with a structure-dependent degree of the contribution from each inhibitory mechanism.
authors: Vicuron Pharmaceuticals Inc., 34790 Ardentech Ct., Fremont, CA 94555, USA. mgordeev@vicuron.com
authors: Mikhail F
authors: MF
authors: Gordeev
authors: Corinne
authors: C
authors: Hackbarth
authors: Michael R
authors: MR
authors: Barbachyn
authors: Lee S
authors: LS
authors: Banitt
authors: James R
authors: JR
authors: Gage
authors: Gary W
authors: GW
authors: Luehr
authors: Marcela
authors: M
authors: Gomez
authors: Joaquim
authors: J
authors: Trias
authors: Sara E
authors: SE
authors: Morin
authors: Gary E
authors: GE
authors: Zurenko
authors: Christian N
authors: CN
authors: Parker
authors: Jonathan M
authors: JM
authors: Evans
authors: Richard J
authors: RJ
authors: White
authors: Dinesh V
authors: DV
authors: Patel
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D015363:Quinolones; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D000069349:Linezolid