Synthesis and antibacterial activity of substituted oxotriazolylphenyl oxazolidinones

A series of 3-(4'-(2'-alkyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-substituted oxazolidinones was designed and synthesized for in vitro antibacterial activity testing against fourteen Gram-negative and six Gram-positive standard organisms. The minimum inhibitory concentration (MIC) was determined by agar dilution at concentrations of 0.10, 0.20, 0.39, 0.78, 1.56, 3.13, 6.25 microg/mL. Different alkyl groups at the 2'-position played an important role in the activity against Gram-positive organisms. (S)-3-(4'-(2'-ethyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-acetamidomethyloxazolidinone was active against Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus enteridis and Streptococcus nonhemolyticus, whereas 2'-methyl, 2'-propyl and 2'-n-butyl counterparts did not show activity at 6.25 microg/mL. Modification of the 5-substitutent of oxazolidinones also affected the activity against Gram-positive organisms. (S)-3-(4'-(2'-ethyl-3'-oxy-1',2',4'-triazolyl)-phenyl)-5-acetamidomethyloxazolidinones was approximately two fold more potent than 5-chloroacetamido, 5-dichloroacetamido and 5-trifluoroacetamido counterparts against Streptococcus enteridis. None of these compounds showed growth inhibition against fourteen Gram-negative organisms at 6.25 microg/mL.