Synthesis of antimicrobial agents. 5. In vivo metabolism of 7-(4-hydroxypiperazin-1-yl)quinolones

Abstract

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazin-1-yl, a 4-hydroxy-3-methylpiperazin-1-yl, and a 4-hydroxy-3,5-dimethylpiperazin-1-yl group was prepared, and their metabolism to corresponding piperazinyl derivatives after oral administration to mice and rats was studied. This reductive metabolism appeared to be more extensive in mice than in rats. Moreover, the introduction of a methyl group into the alpha-position of the 4-hydroxy group depressed the metabolism in both species.

Quinolone Antibacterials

“…N-alkylation with 3chloromethyl-or 3-iodomethy1cephalosporin derivatives (also prepared in situ) leads to dual action cephalosporins (DACs) in which the j3-lactam is linked with the quinolone via the bond of a tertiary amine ( Fig. Splitting back into the quinolone on which they are based is discussed as the reason (UNO et al 1990(UNO et al , 1993. 1994) or of a quaternary ammonium compound (ALBRECHT et a1.…”