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.
Liu
Jidong
J
The Innovation Center of Drugs, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
He
Baoyuan
B
Yu
Aizhen
A
Zhou
Weicheng
W
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D023303:Oxazolidinones