Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 2. Relationship between lipophilicity and antibacterial activity in 5-thiocarbonyl oxazolidinones.
5-Thiourea and 5-dithiocarbamate oxazolidinones were synthesized as a continuation of research on 5-thiocarbonyl oxazolidinone antibacterial agents considering the hydrophobic parameters of the molecule. The structure-activity relationship (SAR) study revealed that the antibacterial activity on 5-thiocarbonyl oxazolidinones was significantly affected by the lipophilicity, especially the calculated log P value and the balance between 5-hydrophilic (or hydrophobic) substituent and hydrophobic (or hydrophilic) substituents on the benzene ring. Some of 5-thiocarbonyl oxazolidinones were found to have good in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).
Tokuyama
R
R
Research and Development Division, Hokuriku Seiyaku Co., Ltd., Katsuyama, Fukui, Japan. organ-hs@mitene.or.jp
Takahashi
Y
Y
Tomita
Y
Y
Tsubouchi
M
M
Yoshida
T
T
Iwasaki
N
N
Kado
N
N
Okezaki
E
E
Nagata
O
O
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004352:Drug Resistance, Microbial; D007202:Indicators and Reagents; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D008055:Lipids; D010080:Oxazoles