Synthesis and antibacterial activity of 1‐(substituted‐benzyl)‐6‐fluoro‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acids and their 6,8‐difluoro analogs

Alkylation of 6,7‐difluoro‐4‐hydroxyquinoline‐3‐carboxylic acid ethyl ester with substituted‐benzyl chlorides gave 1‐(substituted‐benzyl)‐6,7‐difluoro‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acid ethyl esters. Their treatment with piperazine or N ‐methylpiperazine in pyridine yielded 1‐(substituted‐benzyl)‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐7‐(l‐piperazinyl)quinoline‐3‐carboxylic acid ethyl esters which were hydrolyzed with aqueous sodium hydroxide and then acidified with hydrochloric acid afforded the desired 1‐(substituted‐benzyl)‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐7‐(1‐iperazinyl)quinoline‐3‐carboxylic acids. The 6,8‐difluoro analogs were prepared similarly using 6,7,8‐trifluoro‐4‐hydroxyquinoline‐3‐carboxylic acid ethyl ester as a starting material. Some of these quinolones demonstrated fairly good antibacterial activities. Among them, 6‐fluoro‐1‐(4‐fluorophenylmethyl)‐1,4‐dihydro‐7‐(1‐iperazinyl)‐4‐oxoquinoline‐3‐carboxylic acid ( 7d ) and 6,8‐difluoro‐1‐(3‐fluorophenylmethyl)‐1,4‐dihydro‐7‐(1‐piperazinyl)‐4‐oxoquinoline‐3‐carboxylic acid ( 8c ) are two of the best.