Pyridonecarboxylic acids as antibacterial agents. Synthesis and antibacterial activity of 7-(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid and its analogs

Abstract

The title compounds with an amino- and/or hydroxyl-substituted cyclic group at C-7 were prepared with 1-substituted 7-chloro, 7-(ethylsulfonyl)- and 7-(tosyloxy)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids and their ethyl esters with cyclic amines such as 3-aminopyrrolidine. The N-1 substituent includes ethyl, vinyl and 2-fluoroethyl groups. As a result of in vitro and in vivo antibacterial screenings [Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa], 3 compounds, 1-ethyl- and 1-vinyl-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids and 1-vinyl-7-[3-(methylamino)-1-pyrrolidinyl]analog were more active than enoxacin and worthy of further biological study. Structure-activity relationships are discussed.