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 pyrazolidi none antibacterial agents is described. Specifically, the effect of mo dification of the side chain attached to the nitrogen at C-7 was explo red in an attempt to improve the potency and spectrum of activity. Thi s 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 anima l models was explored. This information proved critical for the identi fication of candidates for clinical evaluation.