Novel C-2 substituted carbapenem derivatives. Part IV. Synthesis and biological activity of five membered heteroaromatic derivatives.
The synthesis, antibacterial activity, and stability to human dehydropeptidase-1 (DHP-1) of a novel series of (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-heterocyclylcarbapen-2-em-3-carb oxylates are described. Of the compounds investigated 1,5-disubstituted pyrazol-3-yl and 3-substituted isoxazol-5-yl derivatives have the best combination of antibacterial activity and stability to DHP-1. They are particularly active against community-acquired respiratory tract pathogens and have stabilities to DHP-1 superior to that of meropenem.
Branch
C L
CL
SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, UK.
Burton
G
G
Clarke
G J
GJ
Coulton
S
S
Douglas
J D
JD
Eglington
A J
AJ
Guest
A W
AW
Hinks
J D
JD
Hird
N W
NW
Holland
R K
RK
Hunt
E
E
Knott
S J
SJ
Moss
S F
SF
Naylor
A
A
Pearson
M J
MJ
Takle
A K
AK
D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D008826:Microbial Sensitivity Tests; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D015780:Carbapenems