10.1021/jm00369a011
The research focuses on the synthesis and structure-activity relationships (SAR) of 1,6,7-trisubstituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids, with the aim of identifying potent new antibacterial agents. The study investigates the effects of various substituents at the C-1, C-6, and C-7 positions on the antibacterial activity of these compounds. Key chemicals used include ethyl 1-ethyl-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylate (7a) as a starting material, and various reagents for introducing different functional groups such as nitro, amino, cyano, chloro, and fluoro at the C-6 position, and 1-pyrrolidinyl, 1-piperazinyl, and N-methyl-1-piperazinyl groups at the C-7 position. The most promising compound identified is l-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylic acid (24b), named enoxacin, which exhibits broad and potent in vitro and in vivo antibacterial activity against both Gram-positive and Gram-negative bacteria, along with weak acute toxicity. The study concludes that the presence of a fluoro group at C-6 and a piperazinyl group at C-7 significantly enhances the antibacterial activity, and that modifications at the N-1 position can also influence the activity and toxicity of these compounds.
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