127350-92-9Relevant articles and documents
Oxazolidinone Compounds and Their Uses in Preparation of Antibiotics
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Paragraph 0220; 0221; 0222, (2014/05/25)
The invention belongs to the field of medicaments, and particularly relates to oxazolidinone compounds and their uses in the preparation of antibiotics. A technical problem to be solved by the invention is to provide new oxazolidinone compounds having the structure represented by Formula I. The oxazolidinone compounds of the invention, which are new compounds obtained through numerous screening, have significant antibacterial activity against bacteria such as drug-resistant staphylococcus aureus, fecal coliform bacteria, and streptococcus pneumoniae, while exhibiting low toxicity. The invention provides new options for the development and application of antibiotics.
NOVEL OXAZOLIDINONE COMPOUNDS AS ANTIINFECTIVE AGENTS
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Page/Page column 50, (2009/01/20)
The present invention relates to novel oxazolidinone compounds of formula (I) with antibacterial activity, their pharmaceutically acceptable salts, their stereoisomers, their prodrugs, pharmaceutical compositions comprising the same and to their use as therapeutic agents
Substituent effects on the antibacterial activity of nitrogen-carbon- linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis
Genin, Michael J.,Allwine, Debra A.,Anderson, David J.,Barbachyn, Michael R.,Emmert, D. Edward,Garmon, Stuart A.,Graber, David R.,Grega, Kevin C.,Hester, Jackson B.,Hutchinson, Douglas K.,Morris, Joel,Reischer, Robert J.,Ford, Charles W.,Zurenko, Gary E.,Hamel, Judith C.,Schaadt, Ronda D.,Stapert, Douglas,Yagi, Betty H.
, p. 953 - 970 (2007/10/03)
A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morpholine ring of linezolid (2). These changes resulted in the preparation of compounds with good activity against the fastidious Gram- negative organisms Haemophilus influenzae and Moraxella catarrhalis. The unsubstituted pyrrolyl analogue 3 and the 1H-1,2,3-triazolyl analogue 6 have MICs against H. influenzae = 4 μg/mL and M. catarrhalis = 2 μg/mL. Various substituents were also placed on the azole moieties in order to study their effects on antibacterial activity in vitro and in vivo. Interesting differences in activity were observed for many analogues that cannot be rationalized solely on the basis of sterics and position/number of nitrogen atoms in the azole ring. Differences in activity rely strongly on subtle changes in the electronic character of the overall azole systems. Aldehyde, aldoxime, and cyano azoles generally led to dramatic improvements in activity against both Gram-positive and Gram-negative bacteria relative to unsubstituted counterparts. However, amide, ester, amino, hydroxy, alkoxy, and alkyl substituents resulted in no improvement or a loss in antibacterial activity. The placement of a cyano moiety on the azole often generates analogues with interesting antibacterial activity in vitro and in vivo. In particular, the 3-cyanopyrrole, 4-cyanopyrazole, and 4-cyano-1H-1,2,3- triazole congeners 28, 50, and 90 had S. aureus MICs ≤ 0.5-1 μg/mL and H. influenzae and M. catarrhalis MICs = 2-4 μg/mL. These analogues are also very effective versus S. aureus and S. pneumoniae in mouse models of human infection with ED50s in the range of 1.2-1.9 mg/kg versus 2.8-4.0 mg/kg for the eperezolid (1) control.
