Vancomycin disulfide derivatives as antibacterial agents.
A series of lipidated vancomycin analogues 1 bearing disulfide bonds within their lipid chains was designed and synthesized to optimize their ADME profiles while retaining antibacterial potency. These compounds exhibited good activity against resistant organisms and low accumulation in tissues such as kidney and liver.
Mu
YongQi
Y
Theravance, Inc, 901 Gateway Blvd, South San Francisco, CA 94080, USA. ymu@theravance.com
Nodwell
Matthew
M
Pace
John L
JL
Shaw
Jeng Pyng
JP
Judice
J Kevin
JK
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004220:Disulfides / Q000138:chemical synthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D004220:Disulfides; D014640:Vancomycin