Synthetic antibacterials. VIII . 7‐(1′‐alkylhydrazino)‐1,8‐naphthyridines and related compounds

Synthesis and in vitro antibacterial activity of 7‐(1′‐alkylhydrazino)‐1,8‐naphthyridines related to nalidixic acid were investigated. Namely, treatment of 7‐alkylamino‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acids 1a‐d with sodium nitrite in the presence of hydrochloric acid gave the 1‐ethyl‐1,4‐dihydro‐7‐( N ‐nitrosoalkylamino)‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acids 2a‐d , which upon reacting with zinc dust in acetic acid gave the 7‐(1′‐alkylhydrazino)‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylicacids 3a‐d. The compound 3a was alternately obtained by the reaction of 7‐chloro‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐1,8‐naphth‐yridine‐3‐carboxylic acid ( 4 ) with methylhydrazine. The reaction of 7‐chloro‐4‐hydroxy‐1,8‐naphthyridine‐3‐carboxylic acid ( 5 ) with methylhydrazine gave the 4‐hydroxy‐7‐(1′‐methylhydrazino)‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acid ( 6 ), which upon treatment with alkyl halides afforded the 1‐alkyl‐1,4‐dihydro‐7‐(1′‐methyl‐hydrazino)‐4‐oxo‐1,8‐naphthyridines 3a and 3e‐g. The reaction of the appropriate 3 with ketones gave the corresponding 7‐(1′‐methylalkylidenehydrazino)‐1,8‐naphthyridines 7a‐c and 8a‐b. Among the compounds prepared, certain 3 and 7 exhibited good activity against Gram‐negative bacteria.