Synthesis of antimicrobial agents. 3. Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones

Abstract

A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared. The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives. From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives. Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.

Structure-absorption relationships of a series of 6-fluoroquinolones

“…CNV 8706 displayed, as a differential structure, a hydroxyl group in the aliphatic chain of the nitrogen in position 4 of the piperazine substitute, which seemed to have a negative effect on the absorption process. Overall, these results agreed with other data from the literature (19,22). With the aim of establishing structure-absorption correlations, at first the simple nonlinear hyperbolic correlation between K abs and P was determined, as this was the most suitable function for understanding the absorption process which also had predictive potential (13).…”

Quinolone Antibacterials

“…This is then reacted with 2-amino- 1ethanthiol, 2-amino-1-propanol, or [1,8]naphthyridine 98c carboxylic acids usual reaction conditions, the ethyl esters of the thiazolo-, oxazolo-, and imidazolo[3,2-a] [1,8]naphthyridine carboxylic acids 98a-c are produced (KONDO et al 1990;Fig. This is then reacted with 2-amino- 1ethanthiol, 2-amino-1-propanol, or [1,8]naphthyridine 98c carboxylic acids usual reaction conditions, the ethyl esters of the thiazolo-, oxazolo-, and imidazolo[3,2-a] [1,8]naphthyridine carboxylic acids 98a-c are produced (KONDO et al 1990;Fig.…”

“…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.…”

Bioisoterism Review- An Biological Modification

“…Trivalent ring substitution of sCHd with sNd in the antibacterial agent norfloxacin (18a) resulted in enoxacin (18b) which is also in clinical use for its antibacterial activity [30] (Table 13). …”