New carbon-linked azole oxazolidinones with improved potency and pharmacokinetics.
Substitution of phenyl oxazolidinones with carbon-linked azoles resulted in the discovery of a new class of potent oxazolidinones that have excellent Gram-positive activity. In addition, replacement of the C-5 acetamide side chains with a 4-methyl triazole diminished monoamine oxidase activity. The synthesis and biological evaluation of these compounds are reported.
Hauck
Sheila I
SI
AstraZeneca R&D Boston, Infection Discovery, 35 Gatehouse Park, Waltham, MA 02451, USA. Sheila.Hauck@astrazeneca.com
Cederberg
Christer
C
Doucette
Amanda
A
Grosser
Lena
L
Hales
Neil J
NJ
Poon
Grace
G
Gravestock
Michael B
MB
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D015169:Colony Count, Microbial; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D051381:Rats; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones