Pyridonecarboxylic Acids as Antibacterial Agents. III

Synthesis and Structure-Activity Relationship of 1-(4-Fluorophenyl)- and 1-(2, 4-Difluorophenyl)-6-substituted-4-pyridone-3-carboxylic Acids

Abstract

A series of 1-(4-fluorophenyl)-and 1-(2, 4-difluorophenyl)-4-pyridone-3-carboxylic acid having a substituent at 6-position has been prepared, and their antibacterial activity and urinary recovery in mice were evaluated. Substituents at 6-position remarkably affected the antibacterial activity and urinary recovery. 1''-Methyl-5''-indolyl compounds (4c, 5c) and 4''-methylaminophenyl compound (5f) showed equal or better in vitro activity than 6-(4-dimethylaminophenyl)-1-(4-fluorophenyl)-4-pyridone-3-carboxylic acid (6) and good urinary recovery. However, no compounds showed better in vitro activity than 1-(4-hydroxyphenyl)-6-(2-thianaphthenyl)-4-pyridone-3-carboxylic acid (7). Structure-activity relationship focused on 1-and 6-substituents is also discussed.