- Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
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Substituted quinolone derivatives in which an oxazolidinone, isoxazolinone, or isoxazoline is covalently bonded to a quinolone, methods of using the quinolone derivatives, and pharmaceutical compositions containing the quinolone derivatives are disclosed. Methods of synthesizing these substituted quinolone derivatives are also disclosed, and in particular a method of manufacturing a 7-(2-oxo-1,3-oxazolidin-3-yl)aryl-3-quinolinecarboxylic acid by condensing a 4-(2-oxo-1,3-oxazolidin-5-yl)aryl boronic acid with a 7-halo-quinolone derivative. The quinolone derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.
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- Novel oxazolidinone-quinolone hybrid antimicrobials
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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.
- Gordeev, Mikhail F.,Hackbarth, Corinne,Barbachyn, Michael R.,Banitt, Lee S.,Gage, James R.,Luehr, Gary W.,Gomez, Marcela,Trias, Joaquim,Morin, Sara E.,Zurenko, Gary E.,Parker, Christian N.,Evans, Jonathan M.,White, Richard J.,Patel, Dinesh V.
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p. 4213 - 4216
(2007/10/03)
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- 2-Fluoro-(oxid-thiopyran-4-yl)benzene derivatives
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Compounds that can be used in the synthesis of cyclic sulfur-containing oxazolidinone antibacterial agents include2-Methylpropyl [4-(3,6-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate,4(R)-trans-[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl 3-nitrobenzenesulfonate,1α,4β(S)-N-[[3-[3-Fluoro-4-(tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propanarnide monohydrate,4(R)-3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-(hydroxymethyl)-2-oxazolidinone,4(R)-[3-[3-Fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl 3-nitrobenzenesulfonate.
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- Process to prepare cyclic-sulfur fluorine containing oxazolidinones
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The invention is a process for the preparation of cyclic-sulfur fluorine containing oxazolidinone antibacterial agents which utilizes the important tetrahydrothiopyran-o-fluorinated carbamate of formula (IV)
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- Stereodivergent synthesis of sulfoxide-containing oxazolidinone antibiotics
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Carbamate 5 was prepared under mild conditions via a novel metal-halogen exchange procedure without competing benzyne formation. Selection of an appropriate oxidation/reduction sequence afforded access to either the cis- or trans-1-oxo-4-aryltetrahydrothi
- Gage, James R.,Perrault, William R.,Poel, Toni-Jo,Thomas, Richard C.
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p. 4301 - 4305
(2007/10/03)
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