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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis and antibacterial activity of substituted oxotriazolylphenyl oxazolidinones
Jidong Liu1, Baoyuan He, Aizhen Yu
1The Innovation Center of Drugs, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China.
Abstract:
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.
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