Fluoronaphthyridines as antibacterial agents. 6. Synthesis and structure-activity relationships of new chiral 7-(1-, 3-, 4-, and 6-methyl-2,5-diazabicyclo(2.2.1)heptan-2-yl)naphthyridine analogues of 7-((1R,4R)-2,5-diazabicyclo(2.2.1)heptan-2-yl)-1-(1,1-dimethylethy l)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid. Influence of the configuration on blood pressure in dogs. A quinolone-class effect

• Published in: Journal of medicinal chemistry Vol. 35; no. 15; pp. 2898 - 2909
• Main Authors: Remuzon, P, Bouzard, D, Guiol, C, Jacquet, J-P
• Format: Journal Article
• Language: English
• Published: 01-01-1992
• ISSN: 0022-2623

A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-(1R,4R)-2,5-diazabicyclo(2.2.1)heptan-2-yl)-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7-(1R,4R)-2,5-diazabicyclo(2.2.1)heptan-2-yl)-1-(1,1-dimethylethyl )-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (1a) (BMY 40062). The derivatives 7-((1R,4R,6S)-6-methyl-2,5-diazabicyclo(2.2.1)heptan-2-yl)-1-(1,1- dimethylethyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carb oxylic acid (41) and 7-(1R,4R,6S)-6-methyl-2,5-diazabicyclo(2.2.1)heptan-2-yl)-1-cyclop ropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (49) showed potent in vitro and in vivo antibacterial activity against Gram-positive and Gram-negative bacteria.