Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride.
Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro- 4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.
Chu
D T
DT
Anti-infective Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-3500.
Nordeen
C W
CW
Hardy
D J
DJ
Swanson
R N
RN
Giardina
W J
WJ
Pernet
A G
AG
Plattner
J J
JJ
D042462:4-Quinolones; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015363:Quinolones; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D042462:4-Quinolones; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D007202:Indicators and Reagents; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C054745:temafloxacin