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

Article abstract of DOI:10.1002/jhet.5570350429

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-(1-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-piperazinyl)quinoline- 3-carboxylic acids. The 6,8-difluoro analogs were prepared similarly using 6,7,8-trifluoro-4-hydroxyquinoline-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-piperazinyl)-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.