Structure-activity relationship within a series of pyrazolidinone antibacterial agents. 2. Effect of side-chain modification on in vitro activity and pharmacokinetic parameters.
The structure-activity relationship among a series of novel pyrazolidinone antibacterial agents is described. Specifically, the effect of modification of the side chain attached to the nitrogen at C-7 was explored in an attempt to improve the potency and spectrum of activity. This approach was successful in identifying several compounds having good in vitro profiles. These top candidates were then evaluated for their activity in vivo, and their pharmacokinetic behavior in various animal models was explored. This information proved critical for the identification of candidates for clinical evaluation.
Ternansky
R J
RJ
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46285.
Draheim
S E
SE
Pike
A J
AJ
Counter
F T
FT
Eudaly
J A
JA
Kasher
J S
JS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006207:Half-Life; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011720:Pyrazoles; D013844:Thiazoles; C084126:LY 255262; C068345:LY 193239