Structure-activity relationship (SAR) studies on oxazolidinone antibacterial agents. 3. Synthesis and evaluation of 5-thiocarbamate oxazolidinones.
A series of 5-thiocarbamate oxazolidinones was prepared and tested for in vitro and in vivo antibacterial activities. The results of in vitro antibacterial activity indicated that the 5-thiocarbamate group was a suitable substituent for the activity by the 5-moderate hydrophilicity. The compounds within a favorable logP value range were found to have potent in vitro antibacterial activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Compounds 3a and 4h were superior to linezolid in both in vitro and in vivo potency and were considered to be hopeful compounds. We also discuss the pharmacokinetic properties of several compounds in mice.
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
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; 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; D010080:Oxazoles