Synthesis and Biological Evaluation of New Oral Carbapenems with 1-Methyl-5-oxopyrrolidin-3-ylthio Moiety

The synthesis and biological properties of 1β-methylcarbapenems with 1-methyl-5-oxopyrrolidin-3-ylthio group at the C-2 position were studied. The sodium (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-1-methyl-5-oxopyrrolidin-3-ylthio]-1-carbapen-2-em-3-carboxylate and its (S)-isomer at the 2-position show potent and well-balanced antibacterial activity. The pharmacokinetic parameters of the pivaloyloxymethyl esters of these two carbapenems were compared in mice. The in vivo potency of these carbapenems was compared with that of cefdinir. Good in vivo efficacy of these ester prodrugs reflected the high and prolonged blood levels in parent drugs achieved after oral administration to mice.