Synthetic Antibacterials. VI. 7-[1-Substituted 2-(5-nitro-2-furyl) vinyl]-1, 8-naphthyridines

Abstract

The starting material, ethyl 7-bromomethyl-4-hydroxy-1, 8-naphthyridine-3-carboxylate (2), was prepared by the reaction of ethyl 4-hydroxy-7-methyl-1, 8-naphthyridine-3-carboxylate (1) with bromine. Condensation of 2 with 5-nitrofurfural afforded ethyl 7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-hydroxy-1, 8-naphthyridine-3-carboxylate (3) which was subsequently hydrolized to give 7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-hydroxy-1, 8-naphthyridine-3-carboxylic acid (4). Alkylation of 4 with alkyl iodide provided 1-alkyl-7-[1-bromo-2-(5-nitro-2-furyl) vinyl]-4-oxo-1, 8-naphthyridine-3-carboxylic acid (5 and 6). Nucleophilic displacement of bromine in 4, 5, and 6 afforded the corresponding 7-[1-alkylamino-2-(5-nitro-2-furyl) vinyl]-1, 8-naphthyridine derivative (7-14). Some members of the series display sufficient antibacterial activity in vitro against both Grampositive and Gram-negative bacteria, however, none of them was active as the model compound, 1-ethyl-7-[2-(5-nitro-2-furyl) vinyl]-4-oxo-1, 8-naphthyridine-3-carboxylic acid (15).