Pleuromutilins. Part 1. The identification of novel mutilin 14-carbamates.
A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1). In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant to currently used agents and shows enhanced metabolic stability when compared to earlier pleuromutilin derivatives. Such derivatives therefore have the potential to provide a new class of antibacterial agents for human therapy which address the threat of bacterial resistance.
Brooks
G
G
SmithKline Beecham Pharmaceuticals Research and Development, Discovery Chemistry Europe, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
Burgess
W
W
Colthurst
D
D
Hinks
J D
JD
Hunt
E
E
Pearson
M J
MJ
Shea
B
B
Takle
A K
AK
Wilson
J M
JM
Woodnutt
G
G
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology; D006193:Haemophilus influenzae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000592:standards; D011083:Polycyclic Compounds; D013210:Staphylococcus / Q000187:drug effects*; D000097567:Pleuromutilins
D000900:Anti-Bacterial Agents; D001685:Biological Factors; D002219:Carbamates; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins; C434329:mutilin 14-(N-(4-methoxybenzoyl))-carbamate; C014224:tiamulin